Search

Guatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α-gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O-methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O-methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively. [ABSTRACT FROM AUTHOR]

Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as "ata", "envira", "envira-preta", and "envira-surucucu". In the present work, we investigated the in vitro and in vivo HepG2 cell growth inhibition capacity of D. pycnastera leaf essential oil (EO). The chemical composition of the EO was determined by GC–MS and GC–FID analyses. The alamar blue assay was used to examine the in vitro cytotoxicity of EO in cancer cell lines and non-cancerous cells. In EO-treated HepG2 cells, DNA fragmentation was measured by flow cytometry. The in vivo antitumor activity of the EO was assessed in C.B-17 SCID mice xenografted with HepG2 cells treated with the EO at a dosage of 40 mg/kg. Chemical composition analysis displayed the sesquiterpenes α-gurjunene (26.83%), bicyclogermacrene (24.90%), germacrene D (15.35%), and spathulenol (12.97%) as the main EO constituents. The EO exhibited cytotoxicity, with IC50 values ranging from 3.28 to 39.39 μg/mL in the cancer cell lines SCC4 and CAL27, respectively. The cytotoxic activity of the EO in non-cancerous cells revealed IC50 values of 16.57, 21.28, and >50 μg/mL for MRC-5, PBMC, and BJ cells, respectively. An increase of the fragmented DNA content was observed in EO-treated HepG2 cells. In vivo, EO displayed tumor mass inhibition activity by 47.76%. These findings imply that D. pycnastera leaf EO may have anti-liver cancer properties. [ABSTRACT FROM AUTHOR]

Background: Great biodiversity is a highlight of Brazilian flora. In contrast, the therapeutic potentialities of most species used in folk medicine remain unknown. Several of these species are commonly used to treat cancer. In this study, we investigated the cytotoxic activity of 18 plants from 16 families that are found in the northeast region of Brazil. Methods: The following species were studied: Byrsonima sericea DC. (Malpighiaceae), Cupania impressinervia Acev. Rodr. var. (revoluta) Radlk (Sapindaceae), Duranta repens Linn. (Verbenaceae), Helicostylis tomentosa (Poepp. & Endl) Rusby (Moraceae), Himatanthus bracteatus (A.DC.) Woodson (Apocynaceae), Ipomoea purga (Wender.) Hayne (Convolvulaceae), Ixora coccinea Linn. (Rubiaceae), Mabea piriri Aubl. (Euphorbiaceae), Miconia minutiflora (Melastomataceae), Momordica charantia L. (Cucurbitaceae), Ocotea glomerata (Nees) Mez (Lauraceae), Ocotea longifolia Kunth (Oreodaphne opifera Mart. Nees) (Lauraceae), Pavonia fruticosa (Mill.) Fawc. & Rendle (Malvaceae), Psychotria capitata Ruiz & Pav. (Rubiaceae), Schefflera morototoni (Aubl.) Maguire, Steyerm. & Frodin (Araliaceae), Solanum paludosum Moric. (Solanaceae), Xylopia frutescens Aubl. (Annonaceae) and Zanthoxylum rhoifolium Lam. (Rutaceae). Their dried leaves, stems, flowers or fruits were submitted to different solvent extractions, resulting in 55 extracts. After incubating for 72 h, the cytotoxicity of each extract was tested against tumor cell lines using the alamar blue assay. Results: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata extracts demonstrated the most potent cytotoxic activity. The chloroform soluble fractions of D. repens flowers and the hexane extract of I. coccinea flowers led to the isolation of quercetin and a mixture of α- and ( 3-amyrin, respectively, and quercetin showed moderate cytotoxic activity. Conclusion: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata plants were identified as having potent cytotoxic effects. Further investigations are required to determine the mechanisms of cytotoxicity exhibited and their in vivo activities. This work reinforces the need to understand the therapeutics potentialities of Brazilian medicinal plants. [ABSTRACT FROM AUTHOR]

ABSTRACT Guatteria blepharophylla Mart. (synonym Guatteriopsis blepharophylla Mart.) and Guatteria hispida (R.E. Fr.) Erkens & Maas (synonym Guatteriopsis hispida R.E. Fr.) belong to the Annonaceae family and are found in the Brazilian and Colombian Amazon basin. Both species are popularly known as 'envira' or 'envireira'. In the present study, the leaf essential oils of G. blepharophylla (EOGB) and G. hispida (EOGH) were selected to investigate their cytotoxic effects. Tumour cell lines were treated with increasing concentrations of both essential oils for 72 h and analysed by a methyl-[3H]thymidine incorporation assay. The pro-apoptotic effect of these essential oils was assessed in HepG2 cells by morphological analysis (using haematoxylin/eosin staining and acridine orange/ethidium bromide staining), flow cytometry (cell membrane integrity and internucleosomal DNA fragmentation analysis) and a caspase-3 activation assay after 24 h incubation. Both essential oils displayed potent cytotoxicity in different tumour cell lines. EOGB showed IC50 values from 6.03 to 16.46 µg/ml for HepG2 and K562 cell lines, and EOGH showed IC50 values from 5.45 to 24.89 µg/ml for HepG2 and K562 cell lines, respectively. Cell morphologies consistent with apoptosis and a remarkable activation of caspase-3 were observed in the HepG2 cells treated with essential oils for 24 h. Significant increases in internucleosomal DNA fragmentation without altered membrane integrity were also found. In conclusion, both essential oils investigated were able to inhibit tumour cell proliferation and induce cell death by apoptosis pathways. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Diclinanona calycina R. E. Fries popularly known as "envira", is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen compounds (alkaloids and flavonoids) described for the first time in D. calycina as well as in the genus Diclinanona. The structure of these isolated compounds were established by extensive analysis using 1D/2D-NMR spectroscopy in combination with MS. The isolated alkaloids were identified as belonging to the subclasses: simple isoquinoline, thalifoline (1); aporphine, anonaine (2); oxoaporphine, liriodenine (3); benzyltetrahydroisoquinolines, (S)-(+)-reticuline (4); dehydro-oxonorreticuline (3,4-dihydro-7-hydroxy-6-methoxy-1-isoquinolinyl)(3-hydroxy-4-methoxyphenyl)-methanone) (5); (+)-1S,2R-reticuline Nβ-oxide (6); and (+)-1S,2S-reticuline Nα-oxide (7); tetrahydroprotoberberine, coreximine (8); and pavine, bisnorargemonine (9). While the flavonoids belong to the benzylated dihydroflavones, isochamanetin (10), dichamanetin (11), and a mixture of uvarinol (12) and isouvarinol (13). Compound 5 is described for the first time in the literature as a natural product. The cytotoxic activity of the main isolated compounds was evaluated against cancer and non-cancerous cell lines. Among the tested compounds, the most promising results were found for the benzylated dihydroflavones dichamanetin (10), and the mixture of uvarinol (12) and isouvarinol (13), which presented moderate cytotoxic activity against the tested cancer cell lines (<20.0 µg·mL−1) and low cytotoxicity against the non-cancerous cell line MRC-5 (>25.0 µg·mL−1). Dichamanetin (11) showed cytotoxic activity against HL-60 and HCT116 with IC50 values of 15.78 µg·mL−1 (33.70 µmol·L−1) and 18.99 µg·mL−1 (40.56 µmol·L−1), respectively while the mixture of uvarinol (12) and isouvarinol (13) demonstrated cytotoxic activity against HL-60, with an IC50 value of 9.74 µg·mL−1, and HCT116, with an IC50 value of 17.31 µg·mL−1. These cytotoxic activities can be attributed to the presence of one or more hydroxybenzyl groups present in these molecules as well as the position in which these groups are linked. The cytotoxic activities of reticuline, anonaine and liriodenine have been previously established, with liriodenine being the most potent compound. [ABSTRACT FROM AUTHOR]

Simple Summary: Autophagy is a physiological process characterized by the degradation of the cell components through lysosomes due to stimuli/stress. In this study, we review the challenges and therapeutic opportunities that autophagy presents in the treatment of cancer. We discussed the results of several studies that evaluated autophagy as a therapeutic strategy in cancer, both through the modulation of therapeutic resistance and the death of cancer cells. Moreover, we discussed the role of autophagy in the biology of cancer stem cells and the inhibition of this process as a strategy to overcome resistance and progression of cancer stem cells. Autophagy is a physiological cellular process that is crucial for development and can occurs in response to nutrient deprivation or metabolic disorders. Interestingly, autophagy plays a dual role in cancer cells—while in some situations, it has a cytoprotective effect that causes chemotherapy resistance, in others, it has a cytotoxic effect in which some compounds induce autophagy-mediated cell death. In this review, we summarize strategies aimed at autophagy for the treatment of cancer, including studies of drugs that can modulate autophagy-mediated resistance, and/or drugs that cause autophagy-mediated cancer cell death. In addition, the role of autophagy in the biology of cancer stem cells has also been discussed. [ABSTRACT FROM AUTHOR]

Croton matourensis Aubl. (synonym Croton lanjouwensis Jabl.), popularly known as "orelha de burro", "maravuvuia", and/or "sangrad'água", is a medicinal plant used in Brazilian folk medicine as a depurative and in the treatment of infections, fractures, and colds. In this work, we investigated the chemical composition and in vitro cytotoxic and in vivo antitumor effects of the essential oil (EO) from the leaves of C. matourensis collected from the Amazon rainforest. The EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized qualitatively and quantitatively by gas chromatography coupled to mass spectrometry (GC–MS) and gas chromatography with flame ionization detection (GC–FID), respectively. In vitro cytotoxicity of the EO was assessed in cancer cell lines (MCF-7, HCT116, HepG2, and HL-60) and the non-cancer cell line (MRC-5) using the Alamar blue assay. Furthermore, annexin V-FITC/PI staining and the cell cycle distribution were evaluated with EO-treated HepG2 cells by flow cytometry. In vivo efficacy of the EO (40 and 80 mg/kg/day) was demonstrated in C.B-17 severe combined immunodeficient (SCID) mice with HepG2 cell xenografts. The EO included β-caryophyllene, thunbergol, cembrene, p-cymene, and β-elemene as major constituents. The EO exhibited promising cytotoxicity and was able to cause phosphatidylserine externalization and DNA fragmentation without loss of the cell membrane integrity in HepG2 cells. In vivo tumor mass inhibition rates of the EO were 34.6% to 55.9%. Altogether, these data indicate the anticancer potential effect of C. matourensis. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Salacia impressifolia (Miers) A. C. Smith (family Celastraceae) is a traditional medicinal plant found in the Amazon Rainforest known as "miraruíra", "cipó-miraruíra" or "panu" and is traditionally used to treat dengue, flu, inflammation, pain, diabetes, male impotency, renal affections, rheumatism and cancer. Aim of the study: The aim of this study was to investigate in vitro and in vivo anti-leukemia activity of the stem bark of S. impressifolia in experimental models. Materials and methods: The in vitro cytotoxic activity of extracts, fractions and quinonemethide triterpenes (22-hydroxytingenone, tingenone and pristimerin) from the stem bark of S. impressifolia in cultured cancer cells was determined. The in vivo antitumor activity of the ethyl acetate extract (EAE) and of its fraction (FEAE.3) from the stem bark of S. impressifolia was assessed in C.B-17 severe combined immunodeficient (SCID) mice engrafted with human promyelocytic leukemia HL-60 cells. Results: The extract EAE, its fraction FEAE.3, and quinonemethide triterpenes exhibited potent cytotoxicity against cancer cell lines, including in vitro anti-leukemia activity against HL-60 and K-562 cells. Moreover, extract EAE and its fraction FEAE.3 inhibited the in vivo development of HL-60 cells engrafted in C.B-17 SCID mice. Tumor mass inhibition rates were measured as 40.4% and 81.5% for the extract EAE (20 mg/kg) and for its fraction FEAE.3 (20 mg/kg), respectively. Conclusions: Ethyl acetate extract and its fraction from the stem bark of S. impressifolia exhibit in vitro and in vivo anti-leukemia activity that can be attributed to their quinonemethide triterpenes. These data confirm the ethnopharmacological use of this species and may contribute to the development of a novel anticancer herbal medicine. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Highlights: [•] The essential oil contains (E)-caryophyllene as its major component. [•] The essential oil displays cytotoxicity to tumour cell lines. [•] The essential oil possesses in vivo antitumour action. [ABSTRACT FROM AUTHOR]

Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae), popularly known in Brazil as "mucuíba", "ucuúba", "ucuúba-branca" or "ucuúba do igapó", is a medicinal plant used to treat a variety of diseases, including infections, inflammatory processes and cancer. In the present work, we investigated the chemical constituents and the in vitro and in vivo inhibition of human colon carcinoma HCT116 cells by essential oils obtained from the bark (EOB) and leaves (EOL) of V. surinamensis. EOB and EOL were obtained by hydrodistillation and analyzed via gas chromatography with flame ionization detection and gas chromatography coupled to mass spectrometry. In vitro cytotoxic activity was determined in cultured cancer cells HCT116, HepG2, HL-60, B16–F10 and MCF-7 and in a non-cancerous cell line MRC-5 by the Alamar blue assay after 72 h of treatment. Annexin V/propidium iodide staining, mitochondrial transmembrane potential and cell cycle distribution were evaluated by flow cytometry in HCT116 cells treated with essential oils after 24 and 48 h of treatment. The cells were also stained with May-Grunwald-Giemsa to analyze cell morphology. In vivo antitumor activity was evaluated in C.B-17 SCID mice with HCT116 cells. The main constituents in EOB were aristolene (28.0 ± 3.1%), α-gurjunene (15.1 ± 2.4%), valencene (14.1 ± 1.9%), germacrene D (7.5 ± 0.9%), δ-guaiene (6.8 ± 1.0%) and β-elemene (5.4 ± 0.6%). On the other hand, EOL displayed α-farnesene (14.5 ± 1.5%), β-elemene (9.6 ± 2.3%), bicyclogermacrene (8.1 ± 2.0%), germacrene D (7.4 ± 0.7%) and α-cubebene (5.6 ± 1.1%) as main constituents. EOB showed IC 50 values for cancer cells ranging from 9.41 to 29.52 μg/mL for HCT116 and B16–F10, while EOL showed IC 50 values for cancer cells ranging from 7.07 to 26.70 μg/mL for HepG2 and HCT116, respectively. The IC 50 value for a non-cancerous MRC-5 cell was 34.7 and 38.93 μg/mL for EOB and EOL, respectively. Both oils induced apoptotic-like cell death in HCT116 cells, as observed by the morphological characteristics of apoptosis, externalization of phosphatidylserine, mitochondrial depolarization and fragmentation of internucleosomal DNA. At a dose of 40 mg/kg, tumor mass inhibition rates were 57.9 and 44.8% in animals treated with EOB and EOL, respectively. These data indicate V. surinamensis as possible herbal medicine in the treatment of colon cancer. Image 1 [ABSTRACT FROM AUTHOR]