33 results on '"Rosana Crespo"'
Search Results
2. Cytotoxic Screening and Enhanced Anticancer Activity of Lippia alba and Clinopodium nepeta Essential Oils-Loaded Biocompatible Lipid Nanoparticles against Lung and Colon Cancer Cells
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Boris Rodenak-Kladniew, María Agustina Castro, Rocío Celeste Gambaro, Juan Girotti, José Sebastián Cisneros, Sonia Viña, Gisel Padula, Rosana Crespo, Guillermo Raúl Castro, Stephan Gehring, Cecilia Yamil Chain, and Germán Abel Islan
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essential oils ,solid lipid nanoparticles ,cancer cells ,drug delivery ,biocompatibility ,anticancer mechanisms ,Pharmacy and materia medica ,RS1-441 - Abstract
Plant and herbal essential oils (EOs) offer a wide range of pharmacological actions that include anticancer effects. Here, we evaluated the cytotoxic activity of EO from Lippia alba (chemotype linalool), L. alba (chemotype dihydrocarvone, LaDEO), Clinopodium nepeta (L.) Kuntze (CnEO), Eucalyptus globulus, Origanum × paniculatum, Mentha × piperita, Mentha arvensis L., and Rosmarinus officinalis L. against human lung (A549) and colon (HCT-116) cancer cells. The cells were treated with increasing EO concentrations (0–500 µL/L) for 24 h, and cytotoxic activity was assessed. LaDEO and CnEO were the most potent EOs evaluated (IC50 range, 145–275 µL/L). The gas chromatography–mass spectrometry method was used to determine their composition. Considering EO limitations as therapeutic agents (poor water solubility, volatilization, and oxidation), we evaluated whether LaDEO and CnEO encapsulation into solid lipid nanoparticles (SLN/EO) enhanced their anticancer activity. Highly stable spherical SLN/LaDEO and SLN/CnEO SLN/EO were obtained, with a mean diameter of 140–150 nm, narrow size dispersion, and Z potential around −5mV. EO encapsulation strongly increased their anticancer activity, particularly in A549 cells exposed to SLN/CnEO (IC50 = 66 µL/L CnEO). The physicochemical characterization, biosafety, and anticancer mechanisms of SLN/CnEO were also evaluated in A549 cells. SLN/CnEO containing 97 ± 1% CnEO was highly stable for up to 6 months. An increased in vitro CnEO release from SLN at an acidic pH (endolysosomal compartment) was observed. SLN/CnEO proved to be safe against blood components and non-toxic for normal WI-38 cells at therapeutic concentrations. SLN/CnEO substantially enhanced A549 cell death and cell migration inhibition compared with free CnEO.
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- 2023
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3. Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells
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Boris Rodenak-Kladniew, María Agustina Castro, Rosana Crespo, Marianela Galle, and Margarita García de Bravo
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Linalool ,1,8-Cineole ,Non-small lung cancer cells ,Cytostatic effects ,Reactive oxygen species ,Cell migration ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Linalool and 1,8-cineole are plant-derived isoprenoids with anticancer activities in lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of linalool and 1,8-cineole in lung adenocarcinoma A549 cells.Linalool (0–2.0 mM) and 1,8-cineole (0–8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two monoterpenes were able to induce apoptosis, as observed by the lack of caspase-3 and caspase-9 activation, PARP cleavage, and DNA fragmentation. Linalool, but not 1,8-cineole, increased reactive oxygen species production and mitochondrial membrane potential depolarization. Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by linalool since the antioxidant N-acetyl-L-cysteine prevented both effects. Besides, linalool (2.0 mM) and 1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each monoterpene with simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with simvastatin alone. Our results showed that both monoterpenes might be promising anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for lung cancer therapy.
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- 2020
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4. In Vitro Evaluation of Antiatherogenic Potential of Origanum × Paniculatum, Lippia Alba, Clinopodium Nepeta, and Eucalyptus Globulus Essential Oils
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Castro Agustina, Juan Girotti, Barbara Dumrauf, Boris Rodenak-Kladniew, Maria Zaro, Camila Otero, Sandra Montero Villegas, Margarita Garcia de Bravo, Sonia Viña, and Rosana Crespo
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
5. Insulin-like growth factor 1 gene transfer for sporadic Alzheimer's disease: New evidence for trophic factor mediated hippocampal neuronal and synaptic recovery-based behavior improvement
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Joaquín Pardo, Juliette López Hanotte, María Florencia Zappa Villar, Paula C. Reggiani, and Rosana Crespo
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Male ,Neurons ,Neocortex ,Cognitive Neuroscience ,Neurodegeneration ,Hippocampus ,Biology ,Hippocampal formation ,medicine.disease ,Neuroprotection ,Rats ,Rats, Sprague-Dawley ,Disease Models, Animal ,medicine.anatomical_structure ,Postsynaptic potential ,Alzheimer Disease ,Synaptic plasticity ,medicine ,Animals ,Humans ,Neuron ,Insulin-Like Growth Factor I ,Neuroscience - Abstract
Sporadic Alzheimer's disease (sAD) is the most prevalent neurodegenerative disorder with no cure. Patients typically suffer from cognitive impairment imprinted by irreversible neocortex and hippocampal degeneration with overt synaptic and neuron dysfunction. Insulin-like growth factor 1 (IGF1) has proven to be a potent neuroprotective molecule in animal models of age-related neurodegeneration. In this regard, adenoviral gene transfer aiming at IGF1 brain overexpression has been hitherto an underexplored approach for the sAD treatment. We postulated enhanced IGF1 signaling in the brain as a restorative means in the diseased brain to revert cognitive deficit and restore hippocampal function. We implemented recombinant adenovirus mediated intracerebroventricular IGF1 gene transfer on the streptozotocin (STZ) induced sAD rat model, using 3-month-old male Sprague Dawley rats. This approach enhanced IGF1 signaling in the hippocampus and dampened sAD phosphorylated Tau. We found a remarkable short-term improvement in species-typical behavior, recognition memory, spatial memory, and depressive-like behavior. Histological analysis revealed a significant recovery of immature hippocampal neurons. We additionally recorded an increase in hippocampal microglial cells, which we suggest to exert anti-inflammatory effects. Finally, we found decreased levels of pre- and postsynaptic proteins in the hippocampus of STZ animals. Interestingly, IGF1 gene transfer increased the levels of PSD95 and GAD65/67 synaptic markers, indicating that the treatment enhanced the synaptic plasticity. We conclude that exogenous activation of IGF1 signaling pathway, 1 week after intracerebroventricular STZ administration, protects hippocampal immature neurons, dampens phosphorylated Tau levels, improves synaptic function and therefore performs therapeutically on the sAD STZ model. Hence, this study provides strong evidence for the use of this trophic factor to treat AD and age-related neurodegeneration.
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- 2021
6. DNA and chromosomal damage in Senegalese sole (Solea senegalensis) as side effects of ozone-based water treatment - Contribution to optimization of fish-farming practices
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Sofia Guilherme, R. Serradeiro, Mário Pacheco, Rosana Crespo, DS Azevedo, Ana Marques, and Maria Ana Santos
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Ozone ,Physiology ,DNA damage ,Health, Toxicology and Mutagenesis ,Fish farming ,Aquaculture ,010501 environmental sciences ,Biology ,Toxicology ,01 natural sciences ,Biochemistry ,Chromosomes ,Water Purification ,chemistry.chemical_compound ,Animals ,Solea senegalensis ,0105 earth and related environmental sciences ,Chromosome Aberrations ,business.industry ,04 agricultural and veterinary sciences ,Cell Biology ,General Medicine ,DNA oxidation ,Oxidative Stress ,Fish ,chemistry ,Flatfishes ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,%22">Fish ,Water treatment ,business ,DNA Damage ,RAS - Abstract
The progressive growth of aquaculture implicates a dependence on large water amounts, which are submitted to disinfection processes, namely ozonation. Considering the importance of genomic integrity, it is critical to improve the knowledge on ozone-related genotoxic hazard to organisms reared in recirculating aquaculture systems (RAS) applying ozonation. Therefore, genetic damage induced by ozone exposure in the Senegalese sole (Solea senegalensis) was assessed, combining the comet and the erythrocytic nuclear abnormalities (ENA) assays, reflecting different damage levels, i.e. DNA and chromosomal damage, respectively. Fish were subjected to a daily 6-h ozone (0.15 mg L−1) exposure, repeated for 3 consecutive days, simulating a short-term event of overozonation. To assess the temporal impact of the previous event, the progression of damage was evaluated 7 days later, following transference to ozone-free water or to 0.07 mg L−1 ozone, a routinely adopted level in RAS. Both endpoints pointed to the ozone genotoxic potential, displaying DNA oxidation as a possible mechanism of damage. Overall, the present findings pointed out the genotoxic hazard of ozone to fish, highlighting the importance of these types of studies and contributing to improve aquaculture practices, namely in RAS systems. These early genotoxic signals may be a prelude to negative repercussions on fish health, which may affect the aquaculture productivity. The present findings recommend precautions in relation to accidental or intentional overozonation in fish-farming, even when short-term events are considered. The strategies to mitigate the impact of ozonation in S. senegalensis may include a dietary extra supplementation of antioxidants (regularly, or punctually in cases of overozonation).
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- 2019
7. Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells
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Boris Rodenak-Kladniew, Sabrina Maria Luisa Lavarias, María Agustina Castro, María V. Soberón, and Rosana Crespo
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0301 basic medicine ,Cell Survival ,Acyclic Monoterpenes ,Tumor cells ,Toxicology ,Ciencias Biológicas ,03 medical and health sciences ,0302 clinical medicine ,Humans ,OXIDATIVE STRESS ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Philosophy ,General Medicine ,Hep G2 Cells ,Bioquímica y Biología Molecular ,GLYCOLYTIC PATHWAY ,Oxidative Stress ,030104 developmental biology ,HUMAN TUMOR CELL LINES ,A549 Cells ,ESSENTIAL OILS ,030220 oncology & carcinogenesis ,GERANIOL ,Humanities ,CIENCIAS NATURALES Y EXACTAS - Abstract
Geraniol (GOH), like other plant-derived natural bioactive compounds, has been found to possess antiproliferative properties that are essential to cope with malignant tumors. However, the mechanisms of molecular action are not fully elucidated. The aim of this study was to evaluate the effect of GOH on some oxidative parameters in human tumor cell lines (HepG2 and A549). Cytotoxicity evaluated in cell lines by the MTT assay, genotoxicity by the comet assay, and lipid peroxidation by the TBARS. The activities of antioxidant the enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione- S-transferase (GST), were also analyzed. Additionally, intracellular reactive oxygen species (ROS), nitric oxide, and lactate production were determined in HepG2 cells. Both tumor cell lines showed a clear concentration-dependent response to GOH inseveral of the parameters evaluated. Lipids turned out to be more sensitive than DNA to oxidative damage induced by GOH. TBARS levels increased with respect to control (p
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- 2019
8. Cytotoxic effects of essential oils from four Lippia alba chemotypes in human liver and lung cancer cell lines
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Margarita María García de Bravo, Rosana Crespo, Sandra Montero-Villegas, Boris Rodenak-Kladniew, Marianela Galle, José F. Cicció, María Agustina Castro, and Mónica Patricia Polo
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0301 basic medicine ,Cell cycle checkpoint ,Pharmacology ,Ciencias Biológicas ,Apoptosis - Cell cycle arrest ,03 medical and health sciences ,medicine ,Cytotoxic T cell ,Cell proliferation ,Lippia alba ,Mevalonate pathway - HMGCR ,030102 biochemistry & molecular biology ,biology ,Chemistry ,Cell growth ,fungi ,food and beverages ,Cancer ,General Chemistry ,Bioquímica y Biología Molecular ,biology.organism_classification ,medicine.disease ,Bioavailability ,Apoptosis ,Mevalonate pathway ,CIENCIAS NATURALES Y EXACTAS - Abstract
Essential oils (EOs) from aromatic plants contain molecules that can interfere with diseases such as cancer and are considered attractive because of their widespread use, good bioavailability, low toxicity and affordable cost. EOs from Lippia alba (LaEOs) manifest intraspecific chemical differences in its composition – defined as chemotypes – and is notable for the chemical diversity of their volatile secondary metabolites. We evaluated LaEOs chemotypes cytotoxicity on human cancer culture cells and investigated the mechanisms involved in tagetenone (ta) chemotype cytotoxicity. It exhibited selective cytotoxicity against HepG2 and A549 cells. The mechanism involved cell cycle arrest and apoptosis induction. Tagetenone chemotype (LaEOta) treatment caused 3-hydroxy-3-methylglutaryl-coenzyme A reductase decrease and profound cholesterogenesis inhibition with farnesyl pyrophosphate redirection towards other end products, such as ubiquinone. This work contributes to a clearer understanding of mechanisms of action of LaEOta, thus suggesting that the use of that tagetenone chemotype could provide significant health benefits as a chemopreventive and/or chemotherapeutic agent. Fil: Montero Villegas, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Castro, María Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Cicció Alberti, José Francisco. Universidad de Costa Rica; Costa Rica Fil: Garcia, Margarita Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Polo, Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
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- 2018
9. Citrus reticulatapeel oil inhibits non-small cell lung cancer cell proliferation in culture and implanted in nude mice
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Mónica Patricia Polo, Boris Rodenak-Kladniew, María Agustina Castro, Adriana Raquel Massone, Margarita María García de Bravo, and Rosana Crespo
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0301 basic medicine ,Citrus ,Lung Neoplasms ,Cell cycle checkpoint ,Mice, Nude ,Apoptosis ,Pharmacology ,essential oil ,law.invention ,Ciencias Biológicas ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,A549 ,0302 clinical medicine ,In vivo ,law ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Oils, Volatile ,Carcinoma ,medicine ,Animals ,Humans ,Plant Oils ,Lung cancer ,Cell proliferation ,Essential oil ,Cell Proliferation ,Cell growth ,Cell Cycle ,General Medicine ,Bioquímica y Biología Molecular ,medicine.disease ,030104 developmental biology ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Female ,Citrus reticulata ,Growth inhibition ,CIENCIAS NATURALES Y EXACTAS ,Food Science - Abstract
Non-small cell lung cancer (NSCLC) accounts for most cases of lung cancer. The peel oil of Mandarin Citrus reticulata Blanco cv. Dancy (MPO) is a natural source of essential oils and carotenoids. Volatile and non-volatile lipid compounds were characterized by chromatographic methods. We demonstrate that MPO causes a dose-dependent growth inhibition of NSCLC model cells (A549) in culture and tumour growth in vivo of the same cells implanted in nude mice fed with MPO-supplemented diets. MPO induced cell cycle arrest mainly at the G0/G1 phase and reduced the amount of membrane-bound Ras protein along with apoptosis induction. No toxicological effect was found in liver parameters analysed in treated mice and histopathological analyses of their organs did not show any morphological changes. In conclusion, the data suggest that MPO possesses significant antitumor activity without causing systemic toxicity, proposing it as a dietary supplement that may be helpful in cancer prevention. Fil: Castro, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Massone, Adriana Raquel. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Departamento de Patología. Laboratorio de Patología Especial Veterinaria "Dr. Bernardo Epstein"; Argentina Fil: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: García de Bravo, Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
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- 2018
10. Citrus reticulata peel oil as an antiatherogenic agent: Hypolipogenic effect in hepatic cells, lipid storage decrease in foam cells, and prevention of LDL oxidation
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Rosana Crespo, Luciana Gavernet, Manuel A. Llanos, Boris Rodenak-Kladniew, Maria Ana Castro, and Marianela Galle
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CD36 Antigens ,Citrus ,Endocrinology, Diabetes and Metabolism ,CD36 ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Antioxidants ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Animals ,Humans ,Plant Oils ,Antiatherogenic agent ,Intramolecular Transferases ,Foam cell ,Dyslipidemias ,Hypolipidemic Agents ,Nutrition and Dietetics ,biology ,Chemistry ,Lipid metabolism ,Hep G2 Cells ,Atherosclerosis ,Lipoproteins, LDL ,Molecular Docking Simulation ,Cholesterol ,RAW 264.7 Cells ,Biochemistry ,Fruit ,biology.protein ,Hepatocytes ,lipids (amino acids, peptides, and proteins) ,Mevalonate pathway ,Lipid Peroxidation ,Cardiology and Cardiovascular Medicine ,Lanosterol synthase ,Lipoprotein ,Foam Cells - Abstract
Background and aims Hypercholesterolemia and oxidative stress are two of the most important risk factors for atherosclerosis. The aim of the present work was to evaluate mandarin (Citrus reticulata) peel oil (MPO) in cholesterol metabolism and lipid synthesis, and its antioxidant capacity. Methods and results Incubation of hepatic HepG2 cells with MPO (15–60 μL/L) reduced cholesterogenesis and saponifiable lipid synthesis, demonstrated by [14C]acetate radioactivity assays. These effects were associated with a decrease in a post-squalene reaction of the mevalonate pathway. Molecular docking analyses were carried out using three different scoring functions to examine the cholesterol-lowering property of all the components of MPO against lanosterol synthase. Docking simulations proposed that minor components of MPO monoterpenes, like alpha-farnesene and neryl acetate, as well the major component, limonene and its metabolites, could be partly responsible for the inhibitory effects observed in culture assays. MPO also decreased RAW 264.7 foam cell lipid storage and its CD36 expression, and prevented low-density lipoprotein (LDL) lipid peroxidation. Conclusion These results may imply a potential role of MPO in preventing atherosclerosis by a mechanism involving inhibition of lipid synthesis and storage and the decrease of LDL lipid peroxidation.
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- 2019
11. Bioquímica de la interacción hongo entomopatógeno-cutícula de triatomino
- Author
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Rosana Crespo
- Abstract
Los hongos entomopatógenos son microorganismos enemigos naturales de insectos, que participan en la regulación biológica de los mismos. En la actualidad se han descripto aproximadamente 700 especies de hongos entomopatógenos, incluidas en 100 géneros diferentes. Varias de estas especies, principalmente de los géneros Beauveria y Metarhizium, son producidas en distintos países como bioinsecticidas, para controlar insectos plaga del agro. En relación con el estudio de la enfermedad del Chagas, se han detectado en varios países, cepas de Beauveria bassiana y Metarhizium anisopliae, patógenas a distintas especies de Triatominos. Estos hongos entomopatógenos presentan un gran potencial bioinsecticidas para controlar poblaciones de insectos vectores que habitan en zonas peridomiciliarias, donde no resulta factible la utilización de los insecticidas tradicionales. Estos microorganismos, que ingresan al insecto huésped a través de la superficie cuticular, poseen un gran potencial para el control de insectos hematófagos.
- Published
- 2019
12. Design of microparticles of chia seed oil by using the electrostatic layer-by-layer deposition technique
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Bernd W. K. Diehl, Rosana Crespo, Vanesa Yanet Ixtaina, Mabel Cristina Tomás, Luciana Magdalena Julio, and Claudia Noelia Copado
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Otras Ingenierías y Tecnologías ,General Chemical Engineering ,PHYSICOCHEMICAL STABILITY ,Fraction (chemistry) ,02 engineering and technology ,INGENIERÍAS Y TECNOLOGÍAS ,Chitosan ,Alimentos y Bebidas ,chemistry.chemical_compound ,020401 chemical engineering ,MODIFIED SUNFLOWER LECITHINS ,Monolayer ,BI-LAYERED MICROPARTICLES ,Peroxide value ,0204 chemical engineering ,CHIA SEED OIL ,chemistry.chemical_classification ,Layer by layer ,Ω-3 FATTY ACIDS ,021001 nanoscience & nanotechnology ,Maltodextrin ,Sunflower ,chemistry ,LAYER-BY-LAYER DEPOSITION ,0210 nano-technology ,Polyunsaturated fatty acid ,Nuclear chemistry - Abstract
This study deals with the physicochemical characterization of powdered chia oil microparticles produced from mono and bi-layered emulsions using modified sunflower lecithins (Deoiled (DL); Phosphatidylcholine-enriched fraction (PC)), chitosan, and maltodextrin as wall materials. The powders were stored (20 ± 2 °C, RH 33%, 120d) and characterized by their moisture content, aw, ω-3 content (1H NMR), microencapsulation efficiency of oil (%ME) and ω-3 PUFAs (%MEω-3), microstructure, dispersibility, color, and oxidative stability (Rancimat induction time (ti); Peroxide value (PV)). The %ME were > 84% and %MEω-3 > 89% in all cases, recording systems with DL higher values than those with PC. The bi-layered systems presented higher ti, lower PV and higher %remaining ω-3 than the monolayer ones and the bulk oil. Bi-layered microparticles with modified sunflower lecithins were efficient to protect chia oil against oxidative deterioration, being suitable delivery systems of ω-3 fatty acids from this oil for functional food development. Fil: Julio, Luciana Magdalena. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina Fil: Copado, Claudia Noelia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Diehl, Bernd W. K.. Spectral Service Gmbh Laboratorium Fur Auftragsanalytik; Alemania Fil: Ixtaina, Vanesa Yanet. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina Fil: Tomás, Mabel Cristina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina
- Published
- 2019
13. Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells
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Margarita María García de Bravo, Rosana Crespo, Marianela Galle, Boris Rodenak-Kladniew, and María Agustina Castro
- Subjects
0301 basic medicine ,Cell biology ,Cytotoxicity ,1,8-Cineole ,Cancer research ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Linalool ,Natural product ,purl.org/becyt/ford/1 [https] ,Bioactive plant product ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Chemotherapy ,Cell migration ,Viability assay ,lcsh:Social sciences (General) ,lcsh:Science (General) ,purl.org/becyt/ford/1.6 [https] ,A549 cell ,chemistry.chemical_classification ,Reactive oxygen species ,Multidisciplinary ,Cell growth ,Cytostatic effects ,Chemosensitizers ,Pharmaceutical science ,030104 developmental biology ,chemistry ,Oxidative stress ,Cell culture ,Apoptosis ,Ciencias Médicas ,Non-small lung cancer cells ,lcsh:H1-99 ,030217 neurology & neurosurgery ,lcsh:Q1-390 ,Research Article - Abstract
Linalool and 1,8-cineole are plant-derived isoprenoids with anticancer activities in lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of linalool and 1,8-cineole in lung adenocarcinoma A549 cells. Linalool (0–2.0 mM) and 1,8-cineole (0–8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two monoterpenes were able to induce apoptosis, as observed by the lack of caspase-3 and caspase-9 activation, PARP cleavage, and DNA fragmentation. Linalool, but not 1,8-cineole, increased reactive oxygen species production and mitochondrial membrane potential depolarization. Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by linalool since the antioxidant N-acetyl-L-cysteine prevented both effects. Besides, linalool (2.0 mM) and 1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each monoterpene with simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with simvastatin alone. Our results showed that both monoterpenes might be promising anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for lung cancer therapy., Instituto de Investigaciones Bioquímicas de La Plata
- Published
- 2020
14. 1,8-Cineole promotes G0/G1 cell cycle arrest and oxidative stress-induced senescence in HepG2 cells and sensitizes cells to anti-senescence drugs
- Author
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Rosana Crespo, Boris Rodenak-Kladniew, Marianela Galle, Peter Stärkel, Agustina Castro, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
- Subjects
AMPK ,0301 basic medicine ,Senescence ,Cell cycle checkpoint ,Resting Phase, Cell Cycle ,030226 pharmacology & pharmacy ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,Cell cycle arrest ,03 medical and health sciences ,MAPKs ,0302 clinical medicine ,Humans ,Viability assay ,General Pharmacology, Toxicology and Pharmaceutics ,Protein kinase B ,Cellular Senescence ,PI3K/AKT/mTOR pathway ,Hepatocellular carcinoma cells ,8-Cineole ,Eucalyptol ,Dose-Response Relationship, Drug ,Cell growth ,Chemistry ,TOR Serine-Threonine Kinases ,G1 Phase ,Ribosomal Protein S6 Kinases, 70-kDa ,Cell Cycle Checkpoints ,Hep G2 Cells ,General Medicine ,Akt/mTOR ,Cell cycle ,Oxidative Stress ,030104 developmental biology ,Enzyme Induction ,Cancer research ,Reactive Oxygen Species ,Protein Kinases - Abstract
Aims 1,8-Cineole is a plant-derived monoterpene and a major constituent of Eucalyptus essential oil. Previously, we demonstrated that 1,8-cineole inhibited hepatocellular carcinoma (HCC) HepG2 cell growth. However, the underlying mechanisms remain unknown. Here, we evaluated the mechanisms of action of 1,8-cineole and the potential benefits of its combination with anticancer compounds harboring “anti-senescence” properties in HepG2 cells. Main methods Cell viability was determined by the MTT assay. Cell cycle was assessed through flow cytometry (FC) and western blot (WB). Senescence was determined by the SA-β-galactosidase assay, and apoptosis by caspase-3 activity, WB, and TUNEL. MAPKs (ERK, JNK, and p38), AMPK, and Akt/mTOR were analyzed by WB. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated by FC and fluorescence microscopy. Key findings 1,8-Cineole inhibited cell proliferation by promoting G0/G1 arrest. While 1,8-cineole was unable to trigger apoptosis, it induced cellular senescence. 1,8-Cineole promoted ROS production, ΔΨm depolarization, AMPK, ERK, and p38 activation and mTOR inhibition. Antioxidants, like N-acetyl-L-cysteine and vitamins, prevented HepG2 cell growth inhibition and senescence induced by 1,8-cineole. Pre-incubation with 1,8-cineole sensitized HepG2 cells to the anti-senescence compounds, quercetin, simvastatin, U0126, and SB202190. Combinations of 1,8-cineole and each compound synergistically inhibited cell viability, and combined treatment with 1,8-cineole and simvastatin induced apoptosis. Significance 1,8-Cineole induces G0/G1 arrest and senescence in HepG2 cells through oxidative stress and MAPK, AMPK, and Akt/mTOR pathways, and sensitizes cells to anti-senescence drugs, suggesting that 1,8-cineole has potential as an antineoplastic and adjuvant compound in combination with anti-senescence drugs in HCC therapy.
- Published
- 2020
15. Linalool induces cell cycle arrest and apoptosis in HepG2 cells through oxidative stress generation and modulation of Ras/MAPK and Akt/mTOR pathways
- Author
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Peter Stärkel, Boris Rodenak-Kladniew, Margarita María García de Bravo, Rosana Crespo, Agustina Castro, and Christine De Saeger
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cell cycle checkpoint ,Biología ,Cyclin A ,Apoptosis ,purl.org/becyt/ford/1 [https] ,0302 clinical medicine ,REACTIVE OXYGEN SPECIES ,General Pharmacology, Toxicology and Pharmaceutics ,CELL CYCLE ARREST ,Hepatocellular carcinoma cells ,biology ,Chemistry ,TOR Serine-Threonine Kinases ,Hep G2 Cells ,General Medicine ,Bioquímica y Biología Molecular ,Cell biology ,APOPTOSIS ,RAS/MAPKS ,030220 oncology & carcinogenesis ,AKT/MTOR ,Ras/MAPKs ,CIENCIAS NATURALES Y EXACTAS ,Bioquímica ,Cell Survival ,MAP Kinase Signaling System ,Acyclic Monoterpenes ,Linalool ,General Biochemistry, Genetics and Molecular Biology ,Cell cycle arrest ,Ciencias Biológicas ,03 medical and health sciences ,Humans ,Viability assay ,LINALOOL ,purl.org/becyt/ford/1.6 [https] ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Dose-Response Relationship, Drug ,Cell growth ,Cell Cycle Checkpoints ,Akt/mTOR ,Oxidative Stress ,030104 developmental biology ,Monoterpenes ,ras Proteins ,biology.protein ,Reactive oxygen species ,Proto-Oncogene Proteins c-akt ,HEPATOCELLULAR CARCINOMA CELLS - Abstract
Aims Linalool is a plant-derived monoterpene with anticancer activity, however its mechanisms of action remain poorly understood. The aim of this work was to elucidate the anticancer mechanisms of action of linalool in hepatocellular carcinoma (HCC) HepG2 cells. Main methods Cell viability and proliferation were determined by WST-1 assay and BrdU incorporation, respectively. Cell cycle analysis was assessed through flow cytometry (FC) and western blot (WB). Apoptosis was determined by caspase-3 activity, TUNEL assay and WB. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by FC and fluorescence microscopy. Expression of Ras, MAPKs (ERK, JNK and p38) and Akt/mTOR pathways were evaluated by WB. Key findings Linalool (0–2.5 mM) dose-dependently inhibited cell proliferation by inducing G0/G1 cell cycle arrest, through Cdk4 and cyclin A downregulation, p21 and p27 upregulation, and apoptosis, characterized by MMP loss, caspase-3 activation, PARP cleavage and DNA fragmentation. Low concentrations of linalool (1.0 mM) reduced membrane-bound Ras and Akt activity whereas higher amounts (2.0 mM) triggered mTOR inhibition and ROS generation, in correlation with MAPKs activation and Akt phosphorylation. ROS scavenger N-acetyl-L-cysteine partially rescued HepG2 cell growth and prevented MPP depolarization, ERK and JNK activation. Moreover, specific ERK and Akt phosphorylation inhibitors potentiated linalool anti-cancer activity, pointing Akt and ERK activation as pro-survival mechanisms in response to higher concentrations of linalool. Significance This report reveals that linalool induces G0/G1 arrest and apoptosis in HepG2 cells involving Ras, MAPKs and Akt/mTOR pathways and suggests that linalool is a promising anticancer agent for HCC therapy., Instituto de Investigaciones Bioquímicas de La Plata
- Published
- 2018
16. Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels
- Author
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Sandra Montero Villegas, Ezequiel Lacunza, Boris Emilio Rodenak Kladniew, Marianela Galle, María Agustina Castro, Mónica Patricia Polo, Margarita María García de Bravo, and Rosana Crespo
- Subjects
Very low-density lipoprotein ,Biología ,Gene Expression ,Pharmaceutical Science ,purl.org/becyt/ford/1 [https] ,Mice ,chemistry.chemical_compound ,Drug Discovery ,ACACA ,Cholesterol ,Liver ,Biochemistry ,GERANIOL ,Lipogenesis ,Microsomes, Liver ,Molecular Medicine ,Female ,lipids (amino acids, peptides, and proteins) ,CIENCIAS NATURALES Y EXACTAS ,Sterol Regulatory Element Binding Protein 2 ,medicine.medical_specialty ,Geraniol ,Hypolipemia ,Otras Ciencias Biológicas ,Acyclic Monoterpenes ,Hyperlipidemias ,Biology ,Ciencias Biológicas ,LIPOGENESIS ,Lipid biosynthesis ,Internal medicine ,medicine ,Animals ,HYPOLIPEMIA ,RNA, Messenger ,purl.org/becyt/ford/1.6 [https] ,Triglycerides ,HMGCR ,Pharmacology ,Terpenes ,Acetyl-CoA carboxylase ,HMCGR ,Lipid metabolism ,Lipid Metabolism ,Endocrinology ,Receptors, LDL ,Complementary and alternative medicine ,chemistry ,Ciencias Médicas ,LDL receptor ,Hydroxymethylglutaryl CoA Reductases ,Acetyl-CoA Carboxylase - Abstract
Background: Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. Hypothesis/Purpose: We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. Study Design/Methods: NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [14C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR—the rate-limiting step in cholesterol biosynthesis—along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. Results: Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. Conclusions: The following mechanisms may have mediated the decrease in plasma lipids levels in mice: a down-regulation of hepatocyte-cholesterol synthesis occurred as a result of decreased HMGCR protein levels and catalytic activity; the levels of LDLR mRNA became elevated, thus suggesting an increase in the uptake of serum LDL, especially by the liver; and TG synthesis became reduced very likely because of a decrease in fatty-acid synthesis., Instituto de Investigaciones Bioquímicas de La Plata, Centro de Investigaciones Inmunológicas Básicas y Aplicadas
- Published
- 2015
17. Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils
- Author
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Ana Ves-Losada, Boris Rodenak-Kladniew, María Cecilia Castro, Sandra Montero-Villegas, Marianela Galle, Margarita María García de Bravo, Rosana Crespo, and Mónica Patricia Polo
- Subjects
0301 basic medicine ,Medicina ,Otras Ciencias Biológicas ,Farnesyl pyrophosphate ,Mevalonic Acid ,Cholesterogenesis ,Culture cells ,Biology ,Biochemistry ,Essential oil ,Cell Line ,Ciencias Biológicas ,03 medical and health sciences ,chemistry.chemical_compound ,Squalene ,0302 clinical medicine ,Lipid droplet ,Oils, Volatile ,Humans ,Plant Oils ,Triglycerides ,Ciencias Exactas ,Lippia alba ,CULTURE CELLS ,Cholesterol ,Lanosterol ,Liver cell ,CHOLESTEROGENESIS ,Organic Chemistry ,Cell Biology ,Hep G2 Cells ,biology.organism_classification ,Lipid droplets ,LIPPIA ALBA ,Biosynthetic Pathways ,ESSENTIAL OIL ,030104 developmental biology ,chemistry ,A549 Cells ,030220 oncology & carcinogenesis ,LIPID DROPLETS ,lipids (amino acids, peptides, and proteins) ,Mevalonate pathway ,Lippia ,CIENCIAS NATURALES Y EXACTAS - Abstract
The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L.alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [¹⁴C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2–32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [¹⁴C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic L.alba EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that L.alba EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases., Instituto de Investigaciones Bioquímicas de La Plata, Facultad de Ciencias Exactas
- Published
- 2017
18. A new adenovector system for implementing thymulin gene therapy for inflammatory disorders
- Author
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Mariana Costa, Rosana Crespo, Paula C. Reggiani, Mireille Dardenne, Rodolfo G. Goya, Joaquín Pardo, Maria F. Zappa-Villar, and Micaela López-León
- Subjects
Male ,0301 basic medicine ,Thymic Factor, Circulating ,Genetic enhancement ,medicine.disease_cause ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Transgenes ,Regulation of gene expression ,Chinese hamster ovary cell ,Química ,Doxycycline ,Models, Animal ,Female ,Expression cassette ,Anti-inflammatory peptide ,CIENCIAS NATURALES Y EXACTAS ,medicine.medical_specialty ,Otras Ciencias Biológicas ,Transgene ,Genetic Vectors ,Green Fluorescent Proteins ,Immunology ,CHO Cells ,Biology ,Adenoviridae ,Cell Line ,Ciencias Biológicas ,03 medical and health sciences ,Thymulin ,Cricetulus ,Gene therapy ,Regulatable expression ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Inflammation ,Genetic Therapy ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,chemistry ,Cell culture ,Ciencias Médicas ,Cancer research ,030217 neurology & neurosurgery - Abstract
Thymulin is a thymic peptide possessing anti-inflammatory effects. In order to manipulate thymulin expression in gene therapy studies, we built a bidirectional regulatable two-vector Tet-Off system and the corresponding control system. The experimental two-vector system, ETV, consists of a recombinant adenovector (RAd) harboring an expression cassette centered on a Tet-Off bidirectional promoter flanked by a synthetic gene for thymulin and the gene for humanized Green Fluorescent Protein (hGFP). The second adenovector of this system, RAd-tTA, constitutively expresses the regulatory protein tTA. When cells are co-transduced by the two adenovector components, tTA activates the bidirectional promoter and both transgenes are expressed. In the presence of the antibiotic doxycycline (DOX) transgene expression is deactivated. The control two-vector system, termed CTV, is similar to ETV but only expresses hGFP. In CHO-K1, BHK, and C2C12 cells, ETV and CTV induced a dose-dependent hGFP expression. In CHO-K1 cells, transgene expression was almost completely inhibited by DOX (1 mg/ml). After intracerebroventricular injection of ETV in rats, thymulin levels increased significantly in the cerebrospinal fluid and there was high hGFP expression in the ependymal cell layer. When injected intramuscularly the ETV system induced a progressive increase in serum thymulin levels, which were inhibited when DOX was added to the drinking water. We conclude that our regulatable two-adenovector system is an effective molecular tool for implementing short and long-term anti-inflammatory thymulin gene therapy in animal models of acute or chronic inflammation., Facultad de Ciencias Médicas
- Published
- 2017
19. Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways
- Author
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Martín Carlos Abba, Sandra Montero Villegas, Margarita María García de Bravo, Rosana Crespo, and Mónica Patricia Polo
- Subjects
Transcription, Genetic ,Acyclic Monoterpenes ,Biology ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Phosphatidylcholine Biosynthesis ,Cell Line ,chemistry.chemical_compound ,Biosynthesis ,Humans ,RNA Processing, Post-Transcriptional ,Molecular Biology ,Cell Proliferation ,DNA Primers ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Terpenes ,Cholesterol ,Cell growth ,Cell Biology ,Hep G2 ,Metabolic pathway ,chemistry ,Phosphatidylcholines ,Hydroxymethylglutaryl CoA Reductases ,Mevalonate pathway ,Geraniol - Abstract
Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT–PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [14C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of cholesterol-derived carbon toward other metabolites of the mevalonate pathway. That exogenous mevalonate failed to restore growth in geraniol-inhibited cells suggests that, in addition to the inhibition of HMGCR, other dose-dependent actions exist through which geraniol can impact the mevalonate pathway and consequently inhibit cell proliferation. These results suggest that geraniol, a nontoxic compound found in many fruits and herbs, exhibits notable potential as a natural agent for combatting cancer and (or) cardiovascular diseases.
- Published
- 2013
20. Effect of geraniol on rat cardiomyocytes and its potential use as a cardioprotective natural compound
- Author
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Cecilia Hurtado, Mark Mercola, Boris Rodenak-Kladniew, Rosana Crespo, Pilar Ruiz-Lozano, and Ke Wei
- Subjects
0301 basic medicine ,STRESS ,Endogeny ,Cardioprotection ,Pharmacology ,Research & Experimental Medicine ,medicine.disease_cause ,0601 Biochemistry and Cell Biology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Myocytes, Cardiac ,Pharmacology & Pharmacy ,General Pharmacology, Toxicology and Pharmaceutics ,OXIDATIVE STRESS ,Cells, Cultured ,chemistry.chemical_classification ,ACTIVATED PROTEIN-KINASE ,General Medicine ,APOPTOSIS ,Medicine, Research & Experimental ,NEONATAL RAT CARDIOMYOCYTES ,030220 oncology & carcinogenesis ,GERANIOL ,1115 Pharmacology and Pharmaceutical Sciences ,Life Sciences & Biomedicine ,CIENCIAS NATURALES Y EXACTAS ,Geraniol ,DOXORUBICIN ,Cardiotonic Agents ,Otras Ciencias Biológicas ,Acyclic Monoterpenes ,INHIBITION ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Ciencias Biológicas ,03 medical and health sciences ,CARDIOPROTECTION ,medicine ,Animals ,Neonatal rat cardiomyocytes ,Reactive oxygen species ,Biological Products ,Science & Technology ,Terpenes ,Natural compound ,AMPK ,PATHWAYS ,Hydrogen Peroxide ,Rats ,Oxidative Stress ,030104 developmental biology ,chemistry ,Ischaemic myocardium ,CELLS ,Reactive Oxygen Species ,Oxidative stress - Abstract
Aims Reactive oxygen species (ROS) are generated in the ischaemic myocardium especially during early reperfusion and affect myocardial function and viability. Monoterpenes have been proposed to play beneficial roles in diverse physiological systems; however, the mechanisms of action remain largely unknown. This study aims to assess the effect of monoterpene geraniol (GOH) on neonatal rat ventricular cardiomyocytes (NRVCs) subjected to oxidative stress. Main methods We used an in vitro model of hypoxia-reoxygenation. Cardioprotective (AMPK) and cardiotoxic (ERK1/2, ROS) signaling indicators were measured. Assays were performed by fluorogenic probes, MTT assays and Western-blots. Key findings We determined that the addition of GOH (5–200�μM) to cultured normoxic and hypoxic-NRVCs diminished the endogenous production of ROS in stressed cardiomyocytes. We observed that GOH treatment increased pAMPK levels and decreased pERK1/2 levels in cultured NRVCs. Significance This report suggests that GOH is a candidate cardioprotective natural compound that operates by blunting the oxidative stress signaling that is normally induced by hypoxia-reoxygenation. Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Wei, K.. Tongji University; China Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Mercola, Mark. Stanford Cardiovascular Institute; Estados Unidos. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos Fil: Ruiz Lozano, P.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos. Stanford Cardiovascular Institute; Estados Unidos Fil: Hurtado, C.. Stanford Cardiovascular Institute; Estados Unidos
- Published
- 2016
21. Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line
- Author
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Rosana Crespo, M. G. De Bravo, and Mónica Patricia Polo
- Subjects
Cell growth ,Coenzyme A ,Clinical Biochemistry ,Cell Biology ,General Medicine ,Metabolism ,Pharmacology ,Biology ,Biochemistry ,Hep G2 ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Cell culture ,Simvastatin ,medicine ,lipids (amino acids, peptides, and proteins) ,Geraniol ,medicine.drug - Abstract
Simvastatin is a competitive inhibitor of 3-hydroxymethylglutaryl coenzyme A reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. Both of them inhibit growth and proliferation of many cell lines. The present study was designed to determine the action of geraniol, in combination with simvastatin, by assessing their effects in vitro on human hepatocarcinoma cell line (Hep G2). The treatment of Hep G2 cells with concentrations of simvastatin or geraniol that did not inhibit cell proliferation (5 µmol·l-1 of simvastatin and 50 µmol·l-1 of geraniol) resulted in a significant inhibition of cell proliferation. We also examined the effect of simvastatin, geraniol and the combination of both on the biosynthesis of lipids from [14C]-acetate. Our results demonstrate that the combination of simvastatin and geraniol synergistically inhibited cholesterol biosynthesis and proliferation of Hep G2 cell line, contributing to a better understanding of the action of a component of essential oils targeting a complex metabolic pathway, which would improve the use of drugs or their combination in the fight against cancer and/or cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.
- Published
- 2011
22. Volatile organic compounds released by the entomopathogenic fungus Beauveria bassiana
- Author
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Rosana Crespo, M. P. Juárez, Nicolás Pedrini, and G. M. Dal Bello
- Subjects
Bioquímica ,Entomopathogenic fungi ,Insecta ,Beauveria bassiana ,Solid-phase microextraction ,Mass spectrometry ,Microbiology ,Gas Chromatography-Mass Spectrometry ,Alkanes ,Botany ,Animals ,Beauveria ,Organic Chemicals ,Mycoinsecticides ,Solid Phase Microextraction ,Gas chromatography ,Chromatography ,biology ,fungi ,biology.organism_classification ,Capillary gas chromatography ,Glucose ,Very long chain hydrocarbons ,Entomopathogenic fungus ,Volatilization ,Sesquiterpenes - Abstract
The composition of volatile organic compounds (VOC) released by the entomopathogenic fungus Beauveria bassiana (Hyphomycete: Deuteromycotina) utilizing two different carbon sources was investigated. Analyses were performed by solid-phase microextraction (SPME) coupled to capillary gas chromatography (CGC) and CGC-mass spectrometry (MS). Major components in glucose-grown cultures were diisopropyl naphthalenes, ethanol, and sesquiterpenes. Alkane-grown fungal VOC switched to a fingerprint with prevalence of n-decane. This is the first report on the volatiles released by entomopathogenic fungi., Instituto de Investigaciones Bioquímicas de La Plata, Centro de Investigaciones de Fitopatología
- Published
- 2008
23. Biochemistry of insect epicuticle degradation by entomopathogenic fungi
- Author
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Rosana Crespo, Nicolás Pedrini, and M. Patricia Juárez
- Subjects
Metarhizium ,Physiology ,Health, Toxicology and Mutagenesis ,Cuticle ,media_common.quotation_subject ,ved/biology.organism_classification_rank.species ,Metarhizium anisopliae ,Beauveria bassiana ,Acanthoscelides obtectus ,Insect ,Hyphomycetes ,Toxicology ,Biochemistry ,Microbiology ,Cytochrome P-450 Enzyme System ,Animals ,Triatoma ,Pest Control, Biological ,media_common ,biology ,ved/biology ,fungi ,Cell Biology ,General Medicine ,Peroxisome ,biology.organism_classification ,Sterol ,Insect Vectors ,Coleoptera ,Microscopy, Electron ,Epidermis ,Paecilomyces - Abstract
The biochemical interaction between fungal pathogens and their insect host epicuticle was studied by examining fungal hydrocarbon degrading ability. As a contact insecticide, entomopathogenic fungi invade their host through the cuticle, covered by an outermost lipid layer mainly composed of highly stable, very long chain structures. Strains of Beauveria bassiana and Metarhizium anisopliae (Deuteromycotina: Hyphomycetes), pathogenic both to the blood-sucking bug Triatoma infestans (Hemiptera: Reduviidae) and the bean-weevil Acanthoscelides obtectus (Coleoptera, Bruchidae), were grown on different carbon sources. Alkane-grown cells showed a lipid pattern different from that of glucose-grown cells, evidenced by a major switch in the triacylglycerol and sterol components. Radiolabelled hydrocarbons were used to investigate the catabolic pathway and the by-product incorporation into fungal cellular components. The first oxidation round is presumably carried out by a cytochrome P450 enzyme system, the metabolites will traverse the peroxisomal membrane, and after successive transformations will eventually provide the appropriate fatty acyl CoA for complete degradation in the peroxisomes, the site of β-oxidation in fungi. In this review, we will show the relationship between fungal ability to catabolize very long chain hydrocarbons and virulence parameters.
- Published
- 2007
24. Clues on the role ofBeauveria bassianacatalases in alkane degradation events
- Author
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Maria J. T. de Alaniz, Rosana Crespo, M. Patricia Juárez, and Nicolás Pedrini
- Subjects
0106 biological sciences ,0301 basic medicine ,Physiology ,Cell Biology ,General Medicine ,030108 mycology & parasitology ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Biochemistry ,Genetics ,Alkane degradation ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Published
- 2006
25. Clues on the role of Beauveria bassiana catalases in alkane degradation events
- Author
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Nicolás Pedrini, Maria J. T. de Alaniz, M. Patricia Juárez, and Rosana Crespo
- Subjects
Physiology ,Biology ,chemistry.chemical_compound ,Alkanes ,Genetics ,Beauveria ,Hydrogen peroxide ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Thermostability ,chemistry.chemical_classification ,Molecular mass ,Temperature ,Substrate (chemistry) ,Cell Biology ,General Medicine ,Hydrogen-Ion Concentration ,Peroxisome ,Catalase ,Isoenzymes ,Biodegradation, Environmental ,Enzyme ,chemistry ,Biochemistry ,biology.protein ,Specific activity ,Oxidation-Reduction - Abstract
Entomopathogenic fungi adapt to growth in a culture medium containing an insect-like hydrocarbon as the sole carbon source inducing the beta-oxidation pathway during the alkane degradation. The effect of two carbon sources on the catalase activity was studied in the entomopathogenic fungus Beauveria bassiana. Catalase activity was detected both in the peroxisomal and cytosolic fraction. A significant increment in the specific activity of the peroxisomal fraction (12.6-fold) was observed when glucose was replaced by an insect-like hydrocarbon, whereas the specific activity in the cytosol diminished more than 1.2-fold in the same culture condition. After purification to homogeneity by gel filtration and strong anion exchange chromatography, an apparent molecular mass of 54.7 and 84.0 kDa per subunit were determined respectively for the peroxisomal and cytosolic catalase. The enzymes showed different biochemical and kinetic characteristics, but both were inhibited by 3-amino-1,2,4 triazole. Peroxisomal catalase was sensitive to pH, heat and high concentration of the hydrogen peroxide substrate. Inversely the cytosolic isoform exhibited a broad range of optimal pH (6.0-10.0), high thermostability (
- Published
- 2006
26. [Untitled]
- Author
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Rosana Crespo, G. M. Dal Bello, Susana Beatriz Padín, Nicolás Pedrini, M.P. Júrez, and G. Calderón Fernández
- Subjects
Alkane ,chemistry.chemical_classification ,biology ,ved/biology ,ved/biology.organism_classification_rank.species ,Beauveria bassiana ,Acanthoscelides obtectus ,Hyphomycetes ,biology.organism_classification ,Conidium ,Palmitic acid ,chemistry.chemical_compound ,chemistry ,Animal ecology ,Insect Science ,Botany ,Gas chromatography ,Food science ,Agronomy and Crop Science - Abstract
The effect of alkane-growth induction of theentomopathogenic fungus Beauveria bassiana(Balsamo) Vuillemin (Deuteromycotina:Hyphomycetes), on the ability to kill the beanweevil Acanthoscelides obtectus Say(Coleoptera: Bruchidae), was tested. Adultinsects were sprayed with an 0.01% Tween 20aqueous suspension of 4 × 106 conidia/ml.The performance of fungi grown in complete agarmedium containing glucose as carbon source(FS0) was compared to that of alkane-grownfungi (FS1) with n-hexadecane as the onlycarbon source. Mortality increased (p< 0.05) from 22 ± 4.5% to 44 ±11.4% at day 7, and from 26 ± 5.5% to 60± 7.1% 14 days after treatment withFS0 or FS1 respectively. The insectepicuticular hydrocarbons were analysed bycapillary gas chromatography (CGC); majorcomponents were saturated hydrocarbons, 27 to29 carbons in length. A variety ofmethyl-branched isomers of C27 were theprevailing structures, and nC27 was the majorstraight chain component. Whole insecthydrocarbons were qualitatively identical tothose of the epicuticular surface. Oleic,linoleic and palmitic acids accounted foralmost 88% of the fungal fatty acids,irrespective of the carbon source used forgrowth; however, the unsaturated/saturatedratio diminished markedly from 4.32(FS0) to 2.47 (FS1). These resultsindicate that alkane supplementation of culturemedia might be a tool to improve the virulenceof some mycoinsecticides.
- Published
- 2002
27. Suppression by geraniol of the growth of A549 human lung adenocarcinoma cells and inhibition of the mevalonate pathway in culture and in vivo: potential use in cancer chemotherapy
- Author
-
Sandra Montero Villegas, Mónica Patricia Polo, Boris Emilio Rodenak Kladniew, Marianela Galle, Margarita María García de Bravo, and Rosana Crespo
- Subjects
Cancer Research ,Lung Neoplasms ,Otras Ciencias Biológicas ,Acyclic Monoterpenes ,Medicine (miscellaneous) ,Mevalonic Acid ,Mice, Nude ,Adenocarcinoma of Lung ,Antineoplastic Agents ,Apoptosis ,Biology ,Adenocarcinoma ,Ciencias Biológicas ,chemistry.chemical_compound ,Mice ,A549 ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,geraniol ,Cell Proliferation ,HMGCR ,A549 cell ,Nutrition and Dietetics ,Cell growth ,Terpenes ,cholesterogenesis ,apoptosis ,Xenograft Model Antitumor Assays ,cell proliferation ,Cholesterol ,Oncology ,chemistry ,Biochemistry ,Cell culture ,Cancer cell ,Cancer research ,Female ,Hydroxymethylglutaryl CoA Reductases ,Mevalonate pathway ,Growth inhibition ,CIENCIAS NATURALES Y EXACTAS - Abstract
Geraniol (G)—a natural compound present in the essential oils of many aromatic plants—has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase—the rate-limiting enzyme in cholesterogenesis—in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy. Fil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Montero Villegas, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Garcia, Margarita Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
- Published
- 2014
28. In vitro antitumor activity of N-glycosyl sulfonamides
- Author
-
Margarita María García de Bravo, Rosana Crespo, Rodolfo D. Bravo, and Pedro A. Colinas
- Subjects
Carcinoma, Hepatocellular ,Lung Neoplasms ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Adenocarcinoma ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Glycosyl ,Molecular Biology ,Cell Proliferation ,Antitumor activity ,Sulfonamides ,Organic Chemistry ,Sulfonamide (medicine) ,Diastereomer ,Carbohydrate ,medicine.disease ,In vitro ,chemistry ,Cell culture ,embryonic structures ,Molecular Medicine ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
A series of α- d -hex-2-enopyranosyl sulfonamides was evaluated for their antiproliferative activity against human hepatocellular liver carcinoma (HepG2) and human lung adenocarcinoma (A549) cell lines. The most potent compound (2,4,6-tri- O -acetyl-3-deoxy-α- d - erythro -hex-2-enopyranosyl ethanesulfonamide) showed antiproliferative properties in the micromolar range. The SARs of these sulfonamidoglycoside which includes the influence of carbohydrate rings and sulfonamide class are described.
- Published
- 2010
29. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole, and simvastatin on human cell lines
- Author
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Marianela Galle, Margarita María García de Bravo, Rosana Crespo, Mónica Patricia Polo, Boris Emilio Rodenak Kladniew, and Sandra Montero Villegas
- Subjects
Simvastatin ,linalool ,proliferation ,Otras Ciencias Biológicas ,Acyclic Monoterpenes ,Blotting, Western ,Reductase ,Pharmacology ,Toxicology ,Ciencias Biológicas ,chemistry.chemical_compound ,Linalool ,medicine ,simvastatin ,Humans ,Cell Proliferation ,chemistry.chemical_classification ,Eucalyptol ,Esterification ,Chemistry ,Cell growth ,cholesterogenesis ,Drug Synergism ,General Medicine ,Hep G2 Cells ,Cyclohexanols ,1,8-cineole ,Metabolic pathway ,Enzyme ,Cholesterol ,Biochemistry ,Liver ,Cell culture ,Monoterpenes ,lipids (amino acids, peptides, and proteins) ,Mevalonate pathway ,synergistic effects ,CIENCIAS NATURALES Y EXACTAS ,medicine.drug - Abstract
Monoterpenes are naturally occurring plant hydrocarbons with multiple effects on the mevalonate pathway (MP), while statins competitively inhibit hydroxymethylglutarylcoenzyme-A reductase (HMGCR), the rate-limiting enzyme in the MP. Monoterpenes and statins proved capable of inhibiting both proliferation and cholesterogenesis. In the present study we assess the in vitro antiproliferative and anticholesterogenic effects of two monoterpenes: linalool and 1,8-cineole—either alone, in combination with each other, or combined individually with simvastatin—on liver-derived (HepG2) and extrahepatic (A549) cell lines. The three compounds alone inhibited cell proliferation in a dose-dependent fashion, while their pairwise combination produced synergistic antiproliferative effects in both cell lines. Incorporation experiments with [14C]acetate revealed that linalool and 1,8-cineole inhibited the MP, probably at different points, resulting in a reduction in cholesterogenesis and an accumulation of other MP intermediates and products. Linalool or 1,8-cineole, either together or individually with simvastatin, synergistically inhibited cholesterol synthesis. At low concentrations both monoterpenes inhibited steps specifically involved in cholesterol synthesis, whereas at higher concentrations HMGCR levels became down-regulated. Added exogenous mevalonate failed to reverse the inhibition of proliferation exerted by linalool and 1,8-cineole, suggesting that HMGCR inhibition alone is not responsible for the antiproliferative activity of those agents. This work demonstrates that monoterpenes in combination with each other, or individually in combination with simvastatin synergistically inhibits proliferation and cholesterogenesis in the human cell lines investigated, thus contributing to a clearer understanding of the action of essential-oil components, and their combination with the statins, in the targeting of specific points within a complex metabolic pathway. Fil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Montero Villegas, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Garcia, Margarita Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
- Published
- 2013
30. Study of biochemical biomarkers in freshwater prawn Macrobrachium borellii (Crustacea: Palaemonidae) exposed to organophosphate fenitrothion
- Author
-
Horacio Heras, Nicolás Pedrini, Carlos Fernando Garcia, Sabrina Maria Luisa Lavarias, and Rosana Crespo
- Subjects
Organophosphorous ,Hemocytes ,Health, Toxicology and Mutagenesis ,Hepatopancreas ,Biology ,Fenitrothion ,Toxicology ,Superoxide dismutase ,Ciencias Biológicas ,Lethal Dose 50 ,purl.org/becyt/ford/1 [https] ,chemistry.chemical_compound ,Lipid oxidation ,Hemolymph ,Animals ,Food science ,purl.org/becyt/ford/1.6 [https] ,Organophosphate ,Public Health, Environmental and Occupational Health ,General Medicine ,DNA ,Biomarker ,Bioquímica y Biología Molecular ,biology.organism_classification ,Pollution ,Prawn Toxicity ,Enzyme Activation ,Oxidative Stress ,chemistry ,Catalase ,Prawn ,biology.protein ,Palaemonidae ,Oxidation-Reduction ,CIENCIAS NATURALES Y EXACTAS ,Biomarkers ,Water Pollutants, Chemical - Abstract
Several agrochemicals like organophosphates are extensively used to control pests in agricultural practices but they also adversely affect non-target fauna. The effect of organophosphorous fenitrothion on the prawn Macrobrachium borellii was evaluated. The 96-h LC50 was determined. Activity of superoxide dismutase, catalase, glutathione-S-transferase and lipid oxidation levels, were evaluated in the hepatopancreas from adults exposed to sublethal fenitrothion concentrations for 1, 2, 4 and 7 days. In addition, superoxide dismutase mRNA expression, acetylcholinesterase inhibition and haemocyte DNA damage were determined. The 96-h LC50 was 4.24 μg/l of fenitrothion. Prawn exposed to sublethal FS concentrations showed an increase of both catalase and superoxide dismutase activities, mainly after 2 and 4 days exposure and an increase of glutathione-S-transferase activity from day 2 to day 7 while lipid oxidation levels increased mainly on day 1. Superoxide dismutase transcripts were significantly higher in fenitrothion -treated prawns, indicating an induction mechanism. Hemolymph analysis showed that while acetylcholinesterase activity decreased after 2 days, haemocytes displayed most DNA damage after 7-day exposure to fenitrothion. These results indicate that prawn enzymes are highly sensitive to fenitrothion exposure, and these biological responses in M. borellii could be valuable biomarkers to monitor organophosphorous contamination in estuarine environments. Fil: Lavarias, Sabrina Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; Argentina Fil: Garcia, Carlos Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Pedrini, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina Fil: Heras, Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
- Published
- 2013
31. Cytotoxic and genotoxic effects of defence secretion of Ulomoides dermestoides on A549 cells
- Author
-
M. Patricia Juárez, Alba Mabel Güerci, Juan R. Girotti, M. Luciana Villaverde, Margarita María García de Bravo, and Rosana Crespo
- Subjects
Lung Neoplasms ,Stereochemistry ,Mononuclear cell proliferation ,TENEBRIONIDAE ,GENOTOXICITY ,Antineoplastic Agents ,Pharmacology ,Biology ,medicine.disease_cause ,Cell Line ,Ciencias Biológicas ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Ulomoides dermestoides ,Benzoquinones ,medicine ,Animals ,Humans ,CYTOTOXICITY ,Viability assay ,Cytotoxicity ,Cell Proliferation ,A549 cell ,Carcinoma ,Bioquímica y Biología Molecular ,Coleoptera ,Comet assay ,chemistry ,BENZOQUINONES ,Leukocytes, Mononuclear ,PENTADECENE ,Trypan blue ,ULOMOIDES DERMESTOIDES ,Genotoxicity ,CIENCIAS NATURALES Y EXACTAS ,DNA Damage - Abstract
Ethnopharmacological relevance: Ulomoides dermestoides (Fairmaire, 1893) is a cosmopolitan tenebrionid beetle reared by Argentine people who consume them alive as an alternative medicine in the treatment of different illnesses such as asthma, Parkinson's, diabetes, arthritis, HIV and specially cancer. Aim of the study: To evaluate the cytotoxicity and DNA damage of the major volatile components released by Ulomoides dermestoides on human lung carcinoma epithelial cell line A549. Materials and methods: The defence compounds of Ulomoides dermestoides were extracted with dichloromethane and analyzed and quantified by capillary gas chromatography. The toxicity effects of the beetle's extract against A549 cell line were evaluated. Cytotoxicity was evaluated by MTT test and Trypan blue assay and genotoxicity was evaluated by the comet assay. The synthetic compounds, individually or combined, were also tested in A549 cells and normal mononuclear human cells. Results: The defence compounds of Ulomoides dermestoides extracted with dichloromethane (methyl-1,4-benzoquinones, ethyl-1,4-benzoquinones and 1-pentadecene as major components) showed cytotoxic activity on A549 cells demonstrated by MTT test and Trypan blue assay, with IC 50 values of 0.26 equivalent/ml and 0.34 equivalent/ml, respectively (1 equivalent = amount of components extracted per beetle). The inhibition of A549 cell proliferation with the synthetic blend (1,4-benzoquinone and 1-pentadecene) or 1,4-benzoquinone alone was similar to that obtained with the insect extract. 1-Pentadecene showed no inhibitory effect. Low doses of insect extract or synthetic blend (0.15 equivalent/ml) inhibited mononuclear cell proliferation by 72.2 ± 2.7% and induced significant DNA damage both in tumor and mononuclear cells. Conclusion: Results of this study demonstrated that defence compounds of Ulomoides dermestoides reduced cell viability and induced DNA damage. We also concluded that the insect benzoquinones are primarily responsible for inducing cytotoxicity and genotoxicity in culture cells. Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Villaverde, Maria Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Girotti, Juan Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Güerci, Alba Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Centro de Investigación de Transferencia en Oncología Molecular Argentina; Argentina Fil: Juarez, Marta Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: de Bravo, M.G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
- Published
- 2011
32. Characterization and carbon metabolism in fungi pathogenic to Triatoma infestans, a chagas disease vector
- Author
-
Lázaro F. R. Cafferata, Gustavo Calderón Fernández, M. Patricia Juárez, Roberto E. Lecuona, and Rosana Crespo
- Subjects
chemistry.chemical_classification ,biology ,Linoleic acid ,Metarhizium anisopliae ,Fatty acid ,Metabolism ,biology.organism_classification ,Carbon ,Insect Vectors ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Triatoma infestans ,Saturated fatty acid ,Animals ,Chagas Disease ,Mitosporic Fungi ,Triatoma ,Incubation ,Ecology, Evolution, Behavior and Systematics ,Eicosanoic Acids - Abstract
The pathogenicity of Metarhizium anisopliae (Ma) and Beauveria bassiana (Bb) isolates against Triatoma infestans, the major vector of Chagas disease in Argentina is reported. A 100% mortality was achieved with mean lethal times varying form 5.8 (Ma6) to 7.7 (Bb5) or 11.1 days (Bb10). The fatty acid, hydrocarbon, and total lipid patterns were compared for glucose-grown and alkane-grown Bb10 cultures. The alkane-grown cells showed a lipid pattern different from that of glucose-grown cells, with triacylglyercol as the major lipid fraction, whereas sterols prevailed in the glucose-grown cells. A significant reduction in the relative amounts of linoleic acid diminished the unsaturated/saturated fatty acid ratio for alkane-grown cells; in addition, large amounts of heptacosanoic and eicosanoic acids were detected in the saturated fraction. The hydrocarbon profile of Bb10 showed a saturated chain length distribution,with a marked prevalence for straight chains, ranging from n-C18 to n-C37 in the carbon skeleton, with n-C22 as the major component. Alkane-grown cells showed no qualitative changes in their hydrocarbon fraction, but a similar ratio for odd/even carbon chains. After 48-h incubation assays,[1- 14 C]acetate uptake was largely diminished following a period of alkane growth induction. Glucose-grown cells readily incorporated 19% of the labelinto phospholipids, hydrocarbons, triacylglycerols, and free fatty acids. In contrast, incorporation was reduced to 5.3% for alkane-grown cells, accounting only for phospholipid synthesis.
- Published
- 2000
33. Biochemical Interaction between Entomopathogenous Fungi and Their Insect-Host-like Hydrocarbons
- Author
-
M. Patricia Juárez, Rosana Crespo, and Lázaro F. R. Cafferata
- Subjects
chemistry.chemical_classification ,food.ingredient ,biology ,Physiology ,Catabolism ,Glyceride ,Cuticle ,Metarhizium anisopliae ,Cell Biology ,General Medicine ,biology.organism_classification ,Microbiology ,Acetic acid ,chemistry.chemical_compound ,food ,Hydrocarbon ,chemistry ,Biochemistry ,Genetics ,Agar ,Beauveria ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
The biochemical interaction between fun- gal pathogens and their insect host cuticle was stud- ied by examining fungal hydrocarbon degrading ac- tivity, and the chain length of the lipid metabolites produced. Either n-octacosane or n-tetracosane sub- strate-of like chain length as the epicuticular straight chain hydrocarbons of Triatoma infestans- was used. Metarhizium anisopliae and Beauveria bas- siana strains cultured on glucose-containing agar were able to degrade (3H) octacosane mainly into free fatty acids, phospholipids and acylglycerols. Volatile organic compounds (VOC) were also produced through r3-oxidation reactions. When fungi were in- duced to grow on a hydrocarbon-enriched agar as the sole carbon source, hydrocarbon degrading activity was noticeably increased. The absence of very long chain fatty acids of like carbon skeleton as the sup- plemented hydrocarbon, i.e., the putative direct ox- idation product, together with the large amounts of (3H) acetic acid produced, are supporting evidence for (3-oxidation mechanisms going to completion, thus providing the acetyl-CoA units for de novo syn- thesis of fatty acids. Electron microscopy examination of 3,3'-diaminobenzidine-treated cells showed per- oxisomal proliferation upon alkane-growth induc- tion. These data provide the first insight on fatty acyl metabolites produced by fungal catabolism of insect- derived very long chain alkanes.
- Published
- 2000
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