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Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine's broad-spectrum anticancer activity together with that of three other bisindoles—conophylline, leucophyllidine, and bipleiophylline—against human-derived breast, colorectal, pancreatic, and lung carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (e.g., in MDA-MB-468 breast) or senescence (e.g., in HT-29 colorectal) in cancer cells. Annexin V-FITC/PI, caspase activation, and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Cell cycle perturbations were evident, comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed an induction of aberrant mitotic phenotypes-membrane blebbing, DNA-fragmentation with occasional multi-nucleation. DNA integrity assessment in HCT-116, MDA-MB-468, MIAPaCa-2, and HT-29 cells showed increased fluorescent γ-H2AX during the G1 cell cycle phase; γ-H2AX foci were validated in HCT-116 and MDA-MB-468 cells by confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by increased NQO1 expression. Collectively, we present conofolidine as a putative potent anticancer agent capable of inducing heterogeneous modes of cancerous cell death in vitro, encouraging further preclinical evaluations of this natural product. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma is the most prevalent type of primary liver cancer and remains the foremost cause of cancer-related deaths globally. Dill (Anethum graveolens) seeds, rich in phytoconstituents, is renowned for their pharmacological properties. Objectives: This study performed an in vitro evaluation to assess the cytotoxic effects of dill seed extract (DS-EE) on the Huh-7 hepatocellular carcinoma cell line. Moreover, the study investigated its effects on cell viability, cellular morphology, oxidative damage, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and the expression of apoptosis-related genes in Huh-7 cells. Methods: Huh-7 cells were treated with DS-EE at concentrations ranging from 5 to 100 μg/mL for a duration of 24 h. Results: The cytotoxicity findings showed that DS-EE decreased cell viability and suppressed the growth of Huh-7 cells in a dose-dependent way, with an IC50 value of 60 μg/mL. Exposure to DS-EE extract for 24 h resulted in a significant elevation in lipid peroxidation (LPO) and a notable decrease in glutathione (GSH) content compared to the control. Furthermore, DS-EE significantly increased ROS production while notably decreasing the MMP level in Huh-7 cells. Moreover, DS-EE induces cell apoptosis by upregulating the expression of proapoptotic genes (p53, caspase-3, caspase-9, and Bax) and downregulating the expression of the antiapoptotic gene, Bcl-2. Conclusion: DS-EE exhibited a notable cytotoxic effect on Huh-7 cells by increasing oxidative damage and subsequently modulating the expression of apoptosis-related genes. The results of this study highlight the anticancer effectiveness of DS-EE, indicating its potential as a promising agent for hepatocellular carcinoma management.

Background and purpose: Carbon nanotubes (CNTs) are a significant discovery in nanotechnology, with widespread applications in modern technology. However, there are concerns about their potential toxicity, particularly in skin cells. This study aimed to investigate the mechanisms by which CNTs induced cytotoxicity and apoptosis in mouse skin fibroblasts. Experimental approach: The mice skin fibroblasts were isolated and exposed to two types of CNTs at various concentrations and then analyzed for changes in viability, reactive oxygen species (ROS) production, the levels of Bcl-2-associated X protein (Bax), and lactate production. Findings/Results: The results demonstrated that CNTs reduced cell viability and increased ROS production in a dose-dependent manner. Additionally, the current study found that CNTs increased the protein levels of Bax, a pro-apoptotic protein, in mouse skin fibroblasts. Furthermore, it was observed a significant decrease in lactate production in cells exposed to CNTs. Conclusion and implications: The findings concluded that CNTs have the potential to be toxic substances for skin fibroblasts, which serve as the body's first line of defense. This is evidenced by their ability to increase the production of ROS and the protein levels of Bax, as well as reduce lactic acid levels. As lactic acid has been reported to have beneficial effects on skin collagen production, further studies are needed to fully understand the impact of carbon nanotube exposure on human skin health.

Background and purpose: Carbon nanotubes (CNTs) are a significant discovery in nanotechnology, with widespread applications in modern technology. However, there are concerns about their potential toxicity, particularly in skin cells. This study aimed to investigate the mechanisms by which CNTs induced cytotoxicity and apoptosis in mouse skin fibroblasts. Experimental approach: The mice skin fibroblasts were isolated and exposed to two types of CNTs at various concentrations and then analyzed for changes in viability, reactive oxygen species (ROS) production, the levels of Bcl-2-associated X protein (Bax), and lactate production. Findings/Results: The results demonstrated that CNTs reduced cell viability and increased ROS production in a dose-dependent manner. Additionally, the current study found that CNTs increased the protein levels of Bax, a pro-apoptotic protein, in mouse skin fibroblasts. Furthermore, it was observed a significant decrease in lactate production in cells exposed to CNTs. Conclusion and implications: The findings concluded that CNTs have the potential to be toxic substances for skin fibroblasts, which serve as the body's first line of defense. This is evidenced by their ability to increase the production of ROS and the protein levels of Bax, as well as reduce lactic acid levels. As lactic acid has been reported to have beneficial effects on skin collagen production, further studies are needed to fully understand the impact of carbon nanotube exposure on human skin health. [ABSTRACT FROM AUTHOR]

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research. [ABSTRACT FROM AUTHOR]

Extensive uses of calcium titanate nanoparticles (CaTiO3-NPs) and erbium oxide nanoparticles (Er2O3-NPs) increase their release into the environment and human exposure, particularly through skin contact. However, there are almost no studies available on the effect of these nanoparticles on skin integrity. Therefore, this study was undertaken to estimate CaTiO3-NP- or Er2O3-NP-induced cytotoxicity and genotoxicity in normal human skin fibroblast (HSF) cells. Cell viability was measured using sulforhodamine B (SRB) assay, while the level of DNA damage was detected using the alkaline comet assay. The intracellular levels of reactive oxygen species (ROS) as well as the expression level of p53, Bax, and Bcl2 genes were detected. Although the viability of HSF cells was non-markedly changed after 24 h, prolonged treatment with CaTiO3-NPs or Er2O3-NPs for 72 h induced concentration-dependent death of HSF cells. Treatment of normal HSF cells with IC50/72 h of CaTiO3-NPs or Er2O3-NPs did not cause marked changes in the intracellular level of ROS, DNA damage parameters, and expression levels of apoptosis genes compared to their values in the untreated HSF cells. We thus concluded that CaTiO3-NPs or Er2O3-NPs cause time- and concentration-dependent cytotoxicity toward normal HSF cells. However, safe and non-genotoxic effects were demonstrated by the apparent non-significant changes in intracellular ROS level, DNA integrity, and apoptotic genes' expression after exposure of normal HSF cells to nanoparticles. Thus, it is recommended that further studies be conducted to further understand the toxic and biological effects of CaTiO3-NPs and Er2O3-NPs. [ABSTRACT FROM AUTHOR]

Along with bright fluorescence in the near-IR range, heptamethine carbocyanine dyes possess affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery as covalent conjugates with cytotoxic compounds. To test the properties, structure–activity relationship, and scope of such conjugates, we synthesized drug-dye dyads of tricarbocyanine dyes with anthracycline drug daunorubicin. We used hydrophilic zwitterionic and hydrophobic positively charged benzoindoline-benzothiazole-based heptamethine dyes as terminal alkyne derivatives and N-acylated or oxime-linked daunorubicin as azido-derivatives. These two alkynes and two azides were coupled to each other by Cu-catalyzed Huisgen–Meldal–Sharpless cycloaddition (click reaction) to afford four conjugates. Molecules based on hydrophobic dyes possess submicromolar cytotoxicity to HCT116 cells. Cytotoxicity, cell penetration, intracellular distribution, apoptosis induction and the effect of antioxidants on toxicity were evaluated. The results show that the structure of the cyanine–anthracycline conjugate (hydrophilicity/hydrophobicity, charge, linker, attachment site) is important for its biological activity, thus, expansion of the chemical space of such conjugates could provide new molecular research tools for diagnostics and therapy. [Display omitted] • Four novel daunorubicin-heptamethine cyanine (tricarbocyanine) dye were synthesized. • Conjugates with alkyl-substituted dye posessed micromolar cytotoxicity. • Conjugates with sulfo-substituted dye posessed no cytotoxicity. • Tricarbocyanine delivered anthracycline to mitochondria of cancer cells. • ROS generation contributed to cytotoxicity of the conjugates. [ABSTRACT FROM AUTHOR]

Silica Nanoparticles (SNPs) have been found to exhibit higher cytotoxicity to various cancer cells than to normal cells, while the underlying mechanisms are not fully understood. Here, SNPs triggered much higher cytotoxicity and apoptosis rate in human hepatoma HepG2 cells than in their normal counterparts L-02 cells; we thus selected these two cell lines as the cell model to investigate the mechanisms involved in the SNP-induced selective toxicity to cancer cells. Although uptake pathways and cellular trafficking of SNPs in HepG2 and L-02 cells were similar, more SNPs were taken up and accumulated in the mitochondria of cancer cells. After the removal of free SNPs from the culture medium, nanoparticles were excreted from HepG2 cells more effectively in the first 24 h, but 72 h later more SNPs still remained in cancer cells, leading to the continuous drop in cell viability of HepG2 cells. SNPs triggered a higher ROS generation, along with a lower intracellular GSH content and CAT activity in HepG2 cells than in L-02 cells. This could be due to the fact that HepG2 cells showed a much lower tolerance to H2O2-induced oxidative stress and cell death. Thus, the selective cytotoxicity of SNPs towards cancer cells could probably be explained by the higher particle uptake efficiency and cell sensitivity to oxidative stress as observed in HepG2 cells. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the in vitro cytotoxicity of ethanolic extract of Aloe vera (AVE) against human cancer cell lines. Cytotoxic effect of AVE was evaluated by MTT and NRU assays in human breast (MCF-7) and lung (A-549) cancer cell lines. AVE-induced morphological changes were also visualized under phase contrast microscope. Further, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were detected using DCF-DA and Rh-123 stains, respectively under a fluorescence microscope. Cell cycle progression was measured by flow cytometric analysis. DNA damage was detected by single cell gel electrophoresis (comet assay). The profile of genes related to apoptosis (p53, bax, bcl-2, caspase-3 and -9) was assessed by quantitative real time PCR. AVE exhibited significant cytotoxicity in a dose dependent manner to both MCF-7 and A-549 cells with an IC50 values of 195 μg/mL and 298 μg/mL, respectively. Moreover, AVE induces overproduction of ROS and decreases MMP level in MCF-7 cells. Flow cytometric analysis confirmed that AVE-induced SubG1 cell cycle arrest. The increased p53, bax, capsase-3 and -9 gene expression levels and decreased bcl-2 gene expression level positively correlated AVE-induced MCF-7 cell apoptosis. In conclusion, this study provides mechanistic details of anticancer potential of A. vera. This study also proved that AVE could be a promising anticancer agent in preventing and treating cancer diseases. [ABSTRACT FROM AUTHOR]

The steroidal and terpenoidal composition of Sinularia variabilis was investigated by chromatography methods. One new (1), and four known [gorgasta-5-en-3β-ol (2), ergosta-5-en-3β-ol (3), ergosta-5, 22(Z)-dien-3β-ol (4), 5,8-epidioxy-5α, 8α-ergosta-6, 22E-dien-3β-ol (5)] steroids, in addition to one known diterpenoidal alkaloid [sinulasulfone (6)] isolated for the first time from S. variabilis. If we named the 23-methylergostane core structure as sinustane, new compound (1) was elucidated as 16α,17α-epoxysinusta-5-en-3β–ol-20β-yl sulfate based on NMR and HR Mass data. It was submitted for cytotoxic activity evaluation against MCF-7 and MDA-MB-231 cell lines using MTT assay. Apoptosis induction was checked by flow cytometry (annexin V/propidium iodide) staining. To determine the production of reactive oxygen species, and the mitochondrial transmembrane potential (ΔΨm), the DCFDA, and JC‐1 probes were used in this study. [ABSTRACT FROM AUTHOR]

[Display omitted] Hepatocellular carcinoma is the most prevalent type of primary liver cancer and remains the foremost cause of cancer-related deaths globally. Dill (Anethum graveolens) seeds, rich in phytoconstituents, is renowned for their pharmacological properties. This study performed an in vitro evaluation to assess the cytotoxic effects of dill seed extract (DS-EE) on the Huh-7 hepatocellular carcinoma cell line. Moreover, the study investigated its effects on cell viability, cellular morphology, oxidative damage, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and the expression of apoptosis-related genes in Huh-7 cells. Huh-7 cells were treated with DS-EE at concentrations ranging from 5 to 100 μg/mL for a duration of 24 h. The cytotoxicity findings showed that DS-EE decreased cell viability and suppressed the growth of Huh-7 cells in a dose-dependent way, with an IC 50 value of 60 μg/mL. Exposure to DS-EE extract for 24 h resulted in a significant elevation in lipid peroxidation (LPO) and a notable decrease in glutathione (GSH) content compared to the control. Furthermore, DS-EE significantly increased ROS production while notably decreasing the MMP level in Huh-7 cells. Moreover, DS-EE induces cell apoptosis by upregulating the expression of proapoptotic genes (p53, caspase-3, caspase-9, and Bax) and downregulating the expression of the antiapoptotic gene, Bcl-2. Conclusion: DS-EE exhibited a notable cytotoxic effect on Huh-7 cells by increasing oxidative damage and subsequently modulating the expression of apoptosis-related genes. The results of this study highlight the anticancer effectiveness of DS-EE, indicating its potential as a promising agent for hepatocellular carcinoma management. [ABSTRACT FROM AUTHOR]

Objectives: Aloe perryi plant in the genus Aloe (family: Asphodelaceae), have been used in traditional medicine systems. Herein, we aimed to analyze the anticancer effects of A. perryi petroleum ether extract (APPeE) against human breast cancer (MDA-MB-231) and normal (HEK-293) cell lines. Further the biomarker stigmasterol, isolated from A. perryi extract was quantified by a densitometric high-performance thin layer chromatography (HPTLC) method. Methods: The cytotoxic potential of APPeE was measured by MTT assay, neutral red uptake (NRU) assay, and morphological identification. Results: APPeE-induced a concentration dependent strong cytotoxic effects on MDA-MB-231 cells with an IC50 value of 24.5 μg/ml in contrast to HEK-293 (IC50 value of > 100 μg/ml). Similar results were obtained by NRU assay. Further cytotoxic concentrations of APPeE increased reactive oxygen species (ROS) production and activated caspase-3 and −9, leading to apoptosis in MDA-MB-231 cells. Additionally, a significant augment in the expression of p53, Bax, caspase-3 and −9 with a decline in Bcl-2 gene expression confirmed the involvement of apoptosis pathway in MDA-MB-231 cell death. In HPTLC analysis, the solvent system hexane: ethylacetate (8:2 v/v) furnished a sharp peak for stigmasterol (Rf = 0.19 ± 0.001). The low value of % relative standard deviation (RSD) (0.97–1.39) proposed the method is robust. The limit of detection (LOD) and limit of quantification (LOQ) were established as 13.82 and 41.89 ng, respectively. The stigmasterol in APPeE was quantified as 0.238% w/w of dried APPeE. Conclusions: Hence, this study concludes the promising anticancer effect of APPeE, which might be endorsed to the existence of known anticancer biomarker stigmasterol.

Background: The plant Trigonella foenum graecum, also known as fenugreek, has been shown to have anticancer, antidiabetic, anti-inflammatory, and antioxidant properties. In this study, the hepatoprotective effect of fenugreek seed extract (FSE) against ethanol-induced cell death was investigated in human liver cells (HepG2 and Huh7). Methods and results: The cytotoxic effect of FSE and ethanol on cells was evaluated by exposing the cells at different concentrations. Following that, the cells were pre-incubated with 5–25 μg/ml FSE, followed by a cytotoxic concentration (0.5 mM) of ethanol. MTT and neutral red uptake assays were performed in treated cells to assess the ability of FSE to protect cells from the cytotoxic effects of ethanol. When compared to controls, ethanol treatment significantly reduced the viability of HepG2 and Huh7 cells and altered the cell morphology, whereas treatment with FSE significantly increased cell viability and reversed ethanol-induced morphological changes. Furthermore, pretreatment with FSE dose-dependently reduced lactate dehydrogenate (LDH) leakage, lipid peroxidation (LPO) level, and catalase activities while increasing glutathione (GSH) level induced by ethanol. Pretreatment with FSE also reduced the generation of reactive oxygen species (ROS), caspase enzyme activities, and protein expression of caspase-3 and -9. In HepG2 cells, ethanol-induced apoptosis was observed, whereas FSE treatment reduced apoptosis by downregulating the expression of pro-apoptotic marker genes and upregulating the antiapoptotic gene. Conclusions: In conclusion, this study reports on the mechanistic details of the hepatoprotective potential of FSE. The results also suggest that fenugreek seeds may be useful in preventing liver diseases caused by toxicants such as ethanol. [ABSTRACT FROM AUTHOR]

Verbesina encelioides is known to possess antioxidant, antimicrobial, antidiabetic, and antiviral activities. However, anticancer activity of V. encelioides plant on human colon cancer has not been explored so far. Herein, anticancer potential of ethanolic extract (VE) and aqueous extract (VA) of V. encelioides against human colon cancer cell line (HCT-116) was evaluated. Cell viability assays, morphological analysis, oxidative stress markers (lipid peroxidation (LPO) and glutathione (GSH)), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and apoptotic marker genes were studied. VE exhibited a higher cytotoxic effect related to VA at tested concentrations as observed by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide) (MTT), neutral red uptake (NRU) assays, and morphological analysis. The obtained results showed that VE induced LPO level, GSH depletion, ROS production, and depletion of the mitochondrial membrane potential. A mechanistic study has confirmed that VE induces apoptosis in HCT-116 cells by upregulating pro-apoptotic genes (p53, caspase-3 and − 9, and Bax) expression and downregulating Bcl-2 (antiapoptotic gene). Overall, these results clearly exhibited that VE has anticancer potential against HCT-116 cells through oxidative stress, ROS generation, and mitochondrial-mediated apoptosis. The findings of this study suggest that V. encelioides could be a source for the development of new anticancer agents. [ABSTRACT FROM AUTHOR]

Aims: Endophytes are a rich source for structurally complex chemical scaffolds with interesting biological activities. Endophytes associated with Brugmansia aurea L. (family: Solanaceae), a medicinal plant, have not yet explored for the bioactive metabolites. Method and Results: Hence, Macrophomina phaseolina, a fungal endophyte, was isolated from the roots of the plant. Its methanolic extract was found active against human cancer cell lines with IC50 <20 µg ml−1. Later, a di‐peptide compound, serine‐glycine‐betaine, was isolated and characterized. Serine‐glycine‐betaine consists of a unit of an N‐trimethyl glycine attached to serine. It exhibited potent activity against MIA PaCa‐2 and HCT‐116 cell lines with IC50 8·9 and 15·16 μmol l−1, respectively. Furthermore, it induced apoptosis in MIA PaCa‐2 cells confirmed by microscopy. The apoptotic cell death in MIA PaCa‐2 cells was evidenced biochemically with the generation of intracellular reactive oxygen species level and leading to loss of mitochondrial membrane potential due to activation of the intrinsic pathway. This study describes the plausible biosynthesis of serine‐glycine‐betaine based on genomics (genome sequencing, annotation and genes alignment). Conclusions: A novel di‐peptide, serine‐glycine‐betaine isolated from M. phaseolina induced apoptosis in MIA‐Pa‐Ca‐2 cells. Significance and Impact of the Study: This study confirms that dipeptides like serine‐glycine‐betaine and tyrosine‐betaine might be specific to fungal genera, hence being used for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Anticancer activity of mononuclear Pt(II) complexes bearing organoselenide moiety. [Display omitted] • Syntheses and characterization of four new mononuclear Pt(II) complexes as efficient chemotherapeutic agents. • The complexes were synthesized from heterotridentate coordination core (NOSe) based Schiff bases. • The cytotoxicity of synthesized Pt(II) complexes were examined on MCF-7 and NIH-3T3 cell lines. • ROS generation, flow cytometery and Transwell assays were performed to determine the mechanism of anticancer action. This work features design and syntheses of four mononuclear Pt(II) complexes [Pt(L 1 –H)Cl]; 1, [Pt(L 2 –H)Cl]; 2, [Pt(L 3 –H)Cl]; 3, and [Pt(L 4 –H)Cl]; 4, which were judiciously prepared by tethering with a ONSe donor core of Schiff base ligands (L 1 –L 4). The complexes were fully characterized by IR, NMR spectra, elemental analysis and single crystal X-ray diffraction (sc-XRD) analysis. Notably, cytotoxicity profile of these structurally amended complexes against human breast cancer cell line (MCF-7) and mouse model fibroblast cells (NIH-3T3) cell lines revealed remarkable anticancer activity and selectivity based on their structural activity. [ABSTRACT FROM AUTHOR]

In the environment, tire wear particles (TWPs) could release various additives to induce potential risk, while the effects of particle size on the additive release behavior and ecological risk from TWPs remain unknown. This study investigated the effects and mechanisms of particle sizes (>2 mm, 0.71–1 mm, and <0.1 mm) on the release behavior of TWPs additives under mechanical abrasion and UV irradiation in water. Compared to mechanical abrasion, UV irradiation significantly increased the level of additives released from TWPs. Especially, the additive releasing characteristics were critically affected by the particle sizes of TWPs, manifested as the higher release in the smaller-size ones. After 60 d of UV irradiation, the concentration of antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) reached 10.79 mg/L in the leachate of small-sized TWPs, 2.78 and 5.36 times higher than that of medium-sized and large-sized TWPs. The leachate of the small-sized TWPs also showed higher cytotoxicity. •OH and O 2 •- were identified as the main reactive oxygen species (ROS), which exhibited higher concentrations and dramatic attack on small-sized TWPs to cause pronounced fragmentation and oxidation, finally inducing the higher release of additives. This paper sheds light on the crucial effects and mechanism of particle sizes in the release behavior of TWPs additives, provides useful information to assess the ecological risk of TWPs. [Display omitted] • UV irradiation enhanced the aging and additive release of TWPs relative to mechanical abrasion. • TWPs with small particle sizes (STWPs) released more additives than large-sized ones. • The release of additives is primarily associated with fragmentation and aging of TWPs. • Stronger light absorption of STWPs for generating more •OH and O 2 •- caused the effect. • STWPs displayed higher ecological risks than large-sized ones. [ABSTRACT FROM AUTHOR]

Oxidative stress is known to induce cytotoxicity and apoptosis in endothelial cells and indorse development of atherosclerosis. The aim of this research was to assess the cytoprotective effects of ethanolic extract of Nigella sativa (NSE) against H2O2‐induced cell death in human umbilical vein endothelial cells (HUVECs) and also study the probable mechanisms through which NSE exhibited cyto‐protection. The cytotoxicity was measured by exposing the HUVECs with NSE (10–200 μg/ml) and H2O2 (25–1000 μM) for 24 h. Then, the HUVECs were pretreated with noncytotoxic doses (10–50 μg/ml) of NSE for 24 h before administration of 200 μM H2O2 for 24 h. The MTT, NRU, and morphological assays were performed to assess the cytotoxicity and cyto‐protection. Potential antioxidant activity of NSE on oxidative stress marker (glutathione [GSH] and lipid peroxidation [LPO]) was also evaluated. The fluorescence probe, DCF‐DA, and Rh123 were applied to measure the reactive oxygen species (ROS) level and mitochondrial membrane potential. Moreover, flow cytometric analysis and comet assay were used to study the cell cycle arrest and DNA damage, respectively. The concentrations (10, 30, and 50 μg/ml) of NSE were found to protect HUVECs against H2O2 (200 μM)‐induced cytotoxicity in HUVECs. Pretreatment of HUVECs with NSE significantly reduced the LPO and ROS levels and restored the GSH and loss of MMP induced by H2O2. Furthermore, NSE inhibited H2O2‐induced cell cycle arrest and cellular DNA damage in HUVECs. Altogether, these results suggest that NSE can prevent H2O2‐induced cell death, and NSE could be a potential candidate that can prevent HUVECs against toxicants. The aim of this research was to assess the cytoprotective effects of Nigella sativa (NSE) against H2O2‐induced cell death in human umbilical vein endothelial cells (HUVECs). The concentrations (10, 30, and 50 μg/ml) of NSE were found to protect HUVECs against H2O2 (200 μM)‐induced cytotoxicity in HUVECs. Pretreatment with NSE significantly reduced the LPO and ROS levels and restored the GSH and loss of MMP induced by H2O2. Furthermore, NSE inhibited H2O2‐induced cell cycle arrest and DNA damage in HUVECs. [ABSTRACT FROM AUTHOR]

Copper(I) complexes of the types [Cu(N–N)(PPh3)2]NO3 (LC41–LC44) and [Cu(N–N)(PPh3)(NO3)] (LC45) carrying 3‐substituted 1‐pyridine‐2‐ylimidazo[1,5‐a]pyridine (N–N) derivatives and triphenylphosphine (PPh3) ligands have been prepared. The synthesized copper(I)–phosphine complexes were fully characterized by NMR, IR, ESI‐MS and UV–visible spectroscopy as well as by cyclic voltammetry. Selected structures such as LC42, LC43 and LC45 were additionally analysed by single‐crystal X‐ray method, which show that copper(I) centre adopts a highly distorted tetrahedral geometry. The 1H and 13C NMR spectral data of the complexes throw light on the nature of metal–ligand bonding. They display dπ–π* metal‐to‐ligand charge transfer (MLCT) transition and show quasireversible CuI/CuII metal oxidation. Among the copper(I)–phosphine complexes, LC41–LC44 exhibit moderate cytotoxicity (IC50: 24 h, 67–74 μM; 48 h, 58–70 μM) against human lung epithelial adenocarcinoma A549 cells, whereas LC45 displays the best activity (IC50: 24 h, 42 μM; 48 h, 34 μM) for A549 cancer cell line, which is better than that of the commercial antitumor drug cisplatin. All the complexes also displayed excellent selectivity by being relatively inactive against the human lung epithelial L132 normal cell line with selectivity index (SI) values ranging from 3.4 to 7.4. The complexes block cell cycle progression of A549 cells in G0/G1 phase. FACSVerse analyses are suggestive of reactive oxygen species (ROS) generation and apoptotic cell death induced by the LC41, LC43 and LC45. The induction of apoptosis in A549 cells was shown by Annexin V with propidium iodide (PI) and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining methods and established the ability of LC41, LC43 and LC45 to accumulate in the cell nuclei. [ABSTRACT FROM AUTHOR]

The present study was designed to examine the cytotoxic activity of synthesized single metal oxide nanoparticles such as copper oxide (CuO), iron oxide (γFe2O3) and multi-metal oxide zinc, iron and copper oxide (CuZnFe2O3) in human breast cancer (MCF-7) cells. These single and multi-metal oxide nanoparticles were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The cytotoxic potential of these nanoparticles was assessed by MTT and NRU assays. Further, the morphological alterations, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were also studied. The novelty of the present work express that the MTT and NRU assays revealed a concentration dependent decrease in the viability of MCF-7 cells. The percent cell viability was recorded as 82%, 81%, and 79% in CuFeZn NPs, 81%, 80% and 70% in γFe2O3NPs, 54%, 43% and 27% in CuONPs exposed MCF-7 cells for 24 h at doses 25, 50, 100 μg/ml, respectively by MTT assay. The MTT results was also justified by NRU assay. An increase in ROS generation was observed as 21% and 35% in CuOFeZnNPs, 41% and 61% in γFe2O3NPs and 54% and 89% in CuONPs and the decrease in MMP level was observed as 14% and 24% in CuOFeZn NPs, 37% and 46% in γFe2O3NPs and 52% and 58% in CuONPs at 25 and 50 µg/ml, respectively related to control. Together, these results suggest that the loss of MMP and increase in ROS level could be important mechanism of single and multi-metal oxide nanoparticles induced cytotoxicity in human breast cancer cells. [ABSTRACT FROM AUTHOR]

The widespread application of triazole fungicides makes people attach great concern over its adverse effects in mammalian. In this paper, cytotoxic effects of triazole alcohol fungicides (TAFs) were assessed on human HeLa, A549, HCT116 and K562 cells, and the potential mechanism of TAFs cytotoxicity was studied preliminarily. Results showed that TAFs had cytotoxicity on human cells with different level and cytotoxic selectivity. TAFs cytotoxicity was resonated with a typical hormetic biphasic dose action that produced a complex pattern of stimulatory or inhibitory effects on cell viability. Among the five TAFs, diniconazole revealed a widest range of cytotoxicity to inhibit the viability of the adherent and the suspension cells, causing HeLa cells shrinkage, A549 cells shrunken, and K562 cells collapse, and showed stronger cytotoxicity than hexaconazole. Moreover, the involvement of ROS generation in the cytotoxicity of TAFs on human cells was observed, and the apoptosis of HeLa cells and the formation of apoptotic body in K562 cells induced by diniconazole were characterized. The results indicated the cytotoxicity of TAFs with different structures on human cells was depended on their own property and cell specificity, K562 cells were the most susceptible to TAFs and diniconazole was the strongest toxic. [ABSTRACT FROM AUTHOR]

A number of liver diseases are known to be caused by oxidative stress. Petroselinum sativum (P. sativum; parsley) is popular for its anti-inflammatory, antimicrobial, anticancer, antioxidant and antidiabetic activities. However, till date the hepatoprotective potential of chloroform extract of P. sativum (PSA) on hydrogen peroxide (H2O2) induced cytotoxicity and oxidative stress in human liver (HepG2) cells have not been studied. Therefore, this study was framed to evaluate whether the levels of hydrogen peroxide (H2O2) induced cytotoxicity and oxidative stress in HepG2 cells could be diminished by pretreating the cells with PSA. MTT assay, NRU assay, morphological alterations, glutathione (GSH) depletion, lipid peroxidation (LPO), ROS generation and loss of mitochondrial membrane potential (MMP) were assessed by using non-cytotoxic concentrations (5, 10 and 25 μg/mL) of PSA against H2O2 (0.25 mM) induced damage in HepG2 cells. The results demonstrated that pretreatment of HepG2 cells with PSA offered protective properties by lowering the LPO and ROS generation and elevating the cell viability, GSH and MMP levels. Together, these results suggest that PSA has the hepatoprotective effect on H2O2 induced cell death in HepG2 cells. [ABSTRACT FROM AUTHOR]

Abstract Bismuth oxide nanoparticles (Bi 2 O 3 NPs) have shown great potential for several applications including cosmetics and biomedicine. However, there is paucity of research on toxicity of Bi 2 O 3 NPs. In this study, we first examined dose-dependent cytotoxicity and apoptosis response of Bi 2 O 3 NPs in human breast cancer (MCF-7) cells. We further explored the potential mechanisms of cytotoxicity of Bi 2 O 3 NPs through oxidative stress. Physicochemical study demonstrated that Bi 2 O 3 NPs have crystalline structure and spherical shape with mean size of 97 nm. Toxicity studies have shown that Bi 2 O 3 NPs reduce cell viability and induce membrane damage dose-dependently in the concentration range of 50–300 μg/ml. Bi 2 O 3 NPs also disturbed cell cycle of MCF-7 cells. Oxidative stress response of Bi 2 O 3 NPs was evident by generation of reactive oxygen species (ROS), higher lipid peroxidation, reduction of glutathione (GSH) and low superoxide dismutase (SOD) enzyme activity. Interestingly, supplementation of external antioxidant N-acetyl-cysteine almost negated the effect of Bi 2 O 3 NPs induced oxidative stress and cell death. We also found that exposure of Bi 2 O 3 NPs induced apoptotic response in MCF-7 cells suggested by impaired regulation of Bcl-2, Bax and caspase-3 genes. Altogether, we found that Bi 2 O 3 NPs induced cytotoxicity in MCF-7 cells through modulating the redox homeostasis via Bax/Bcl-2 pathway. This study warranted further research to delineate the underlying mechanism of Bi 2 O 3 NPs induced toxicity at in vivo level. Graphical abstract Image 1 Highlights • Dose-dependent cytotoxicity was observed in Bi 2 O 3 NPs treated MCF-7 cells. • Bi 2 O 3 NPs induced ROS generation, lipid peroxidation and GSH depletion. • Cytotoxicity of Bi 2 O 3 NPs was found to be mediated through oxidative stress. • Bi 2 O 3 NPs exposure impaired the regulation of genes associated with apoptosis. [ABSTRACT FROM AUTHOR]

Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18–65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC50: 41 µM), and induced a general dose-dependent depletion of polyunsaturated lipids (10–20 µM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tri- tert -butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects. [ABSTRACT FROM AUTHOR]

Although InP/ZnS quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based QDs, their toxicity has not been fully understood. In this work, we report the cytotoxicity of InP/ZnS QDs with different surface groups (NH2, COOH, OH) toward two lung-derived cell lines. The diameter and the spectra of InP/ZnS QDs were characterized and the hydrodynamic size of QDs in aqueous solution was compared. The confocal laser scanning microscopy was applied to visualize the labeling of QDs for human lung cancer cell HCC-15 and Alveolar type II epithelial cell RLE-6TN. The flow cytometry was used to confirm qualitatively the uptake efficiency of QDs, the cell apoptosis and ROS generation, respectively. The results showed that in deionized water, InP/ZnS-OH QDs were easier to aggregate, and the hydrodynamic size was much greater than the other InP/ZnS QDs. All these InP/ZnS QDs were able to enter the cells, with higher uptake efficiency for InP/ZnS-COOH and InP/ZnS-NH2 at low concentration. High doses of InP/ZnS QDs caused the cell viability to decrease, and InP/ZnS-COOH QDs and InP/ZnS-NH2 QDs appeared to be more toxic than InP/ZnS-OH QDs. In addition, all these InP/ZnS QDs promoted cell apoptosis and intracellular ROS generation after co-cultured with cells. These results suggested that appropriate concentration and surface functional groups should be optimized when InP/ZnS QDs are utilized for biological imaging and therapeutic purpose in the future.

Dioscorea villosa, commonly known as “Wild Yam” and native to North America, is well documented for its pharmacological properties due to the presence of steroidal glycosides. However, the hepatoprotective potential of these compounds has not been studied so far. The present investigation was aimed to study the hepatoprotective effect of the steroidal glycosides from D. villosa against H2O2, a known hepatotoxin, in human liver cell line (HepG2). Cytotoxicity assessment was carried out in cells exposed to various concentrations (10–50 μM) of compounds for 24 h using MTT assay and morphological changes. All tested compounds were known and among them, spirostans (zingiberensis saponin I, dioscin, deltonin and progenin III) were found to be cytotoxic whereas, furostans (huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin) were non-cytotoxic. Further, HepG2 cells were pretreated with biologically safe concentrations (10, 30, and 50 μM) of non-cytotoxic compounds and then cytotoxic (0.25 mM) concentration of H2O2. After 24 h, cell viability was assessed by MTT and NRU assays, while morphological changes were observed under the microscope. The results showed that treatment of HepG2 cells with compounds prior to H2O2 exposure effectively increased cell viability in a concentration-dependent manner. Furthermore, huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin at 50 μM increased GSH level and decreased intracellular ROS generation against H2O2-induced damages. The results from this study revealed that compounds isolated from D. villosa have hepatoprotective potential against H2O2-induced cytotoxicity and ROS generation and could be promising as potential therapeutic agents for liver diseases.

ZnO NPs (zinc oxide nanoparticles) has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species) production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

Background/purpose: Cigarette smoking is an important risk factor in the pathogenesis of periodontal disease. However, little is known about the effect of nicotine, the major component of cigarette smoke, on cementoblasts. The aim of this study was to investigate the pathological effects of nicotine on the murine immortalized cementoblast cell line (OCCM.30). Materials and methods: Cell viability was judged by using the Alamar Blue reduction assay. Cell migration was evaluated by transwell and wound-healing assays. The protein concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by using enzyme linked immunosorbent assay (ELISA). The semiquantitative 2′,7′-dichlorfluorescein-diacetate (DCFH-DA) fluorescence technique was used to detect the intracellular level of reactive oxygen species (ROS). Results: Concentrations of nicotine > 1.5mM demonstrated cytotoxicity to cementoblasts (P

Dioscorea villosa, commonly known as “Wild Yam” and native to North America, is well documented for its pharmacological properties due to the presence of steroidal glycosides. However, the hepatoprotective potential of these compounds has not been studied so far. The present investigation was aimed to study the hepatoprotective effect of the steroidal glycosides from D. villosa against H2O2, a known hepatotoxin, in human liver cell line (HepG2). Cytotoxicity assessment was carried out in cells exposed to various concentrations (10–50 μM) of compounds for 24 h using MTT assay and morphological changes. All tested compounds were known and among them, spirostans (zingiberensis saponin I, dioscin, deltonin and progenin III) were found to be cytotoxic whereas, furostans (huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin) were non-cytotoxic. Further, HepG2 cells were pretreated with biologically safe concentrations (10, 30, and 50 μM) of non-cytotoxic compounds and then cytotoxic (0.25 mM) concentration of H2O2. After 24 h, cell viability was assessed by MTT and NRU assays, while morphological changes were observed under the microscope. The results showed that treatment of HepG2 cells with compounds prior to H2O2 exposure effectively increased cell viability in a concentration-dependent manner. Furthermore, huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin at 50 μM increased GSH level and decreased intracellular ROS generation against H2O2-induced damages. The results from this study revealed that compounds isolated from D. villosa have hepatoprotective potential against H2O2-induced cytotoxicity and ROS generation and could be promising as potential therapeutic agents for liver diseases. [ABSTRACT FROM AUTHOR]

We describe the synthesis of three new manganese (II) complexes containing the bidentate ligands 2-(1-methyl-3-pyrazolyl)pyridine (pypz-Me) and ethyl 2-(3-(pyridine-2-yl)-1H–pyrazol-1-yl)acetate (pypz-CH 2 COOEt), with formula [MnX 2 (pypz-Me) 2 ] (X = Cl − 1 , CF 3 SO 3 − 2 ) and [Mn(CF 3 SO 3 ) 2 (pypz-CH 2 COOEt) 2 ] 3 . Complexes 1 – 3 have been characterized through analytical, spectroscopic and electrochemical techniques, as well as by monocrystal X-ray diffraction analysis. The complexes show a six-coordinated Mn(II) ion though different stereoisomers have been isolated for the three compounds. Complexes 1 – 3 , together with the previously described compounds [MnCl 2 (pypz-H) 2 ] 4 , [Mn(CF 3 SO 3 ) 2 (pypz-H) 2 ] 5 , [Mn(NO 3 ) 2 (pypz-H) 2 ] 6 , [MnCl 2 (H 2 O) 2 (pypz-H) 2 ] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and ([Mn(CF 3 SO 3 ) 2 ((−)-L) 2 ] 8 , ((−)-L = (−)-pinene[5,6]bipyridine), were tested in vitro for cytotoxic activity against NCI-H460 and OVCAR-8 cancer cell lines. The geometry of a specific compound does not seem to influence its activity in a significant extent. However, among the tested compounds those that display hydrophobic substituents on the pyrazole ring and triflate ions as labile ligands show the best antiproliferative properties. Specifically, compound 8 containing the pinene-bipyridine ligand presents an antiproliferative activity similar to that of cisplatin and higher than that of carboplatin, and displays selectivity for tumour cells. Its antiproliferative effect is due to the generation of ROS species that allow the compound to interact with DNA. [ABSTRACT FROM AUTHOR]

• Quinoline and isoquinoline alkaloids evaluated against Trypanosoma evansi. • Concentration dependent anti-trypanosomal activity and cytotoxicity observed. • Quinine, berbamine and emetine showed higher apoptotic effects among six. • Dose-dependent and time dependent ROS generation observed in treated parasites. Trypanosoma evansi , a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC 50 /24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC 50 to IC 50. Among the selected alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in reactive oxygen species (ROS) production. Therefore, increased apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi -infected mice model. [Display omitted] [ABSTRACT FROM AUTHOR]

Acrylamide (AA) toxicity remains an interesting subject in toxicological research. The aim of the research performed in this paper was to determine mechanisms of cyto- and genotoxic effects of AA on the human colon adenocarcinoma cell line Caco-2, to estimate the inhibitory concentration (IC)50 values in cell viability assays, to measure the basal and oxidative DNA damage as well as the oxidative stress leading to apoptosis, and to assess the morphological changes in cells using microscopic methods. It has been proven that AA induces cytotoxic and genotoxic effects on Caco-2 cells. Higher cytotoxic activity was gained in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay compared with the PrestoBlue assay, with IC50 values of 5.9 and 8.9 mM after 24 h exposure, respectively. In the single-cell gel electrophoresis assay, the greatest DNA damage was caused by the highest concentration of acrylamide equal to 12.5 mM (89.1% ± 0.9%). AA also induced oxidative DNA damage and generated reactive oxygen species (ROS), which was concentration dependent and correlated with the depletion of mitochondrial membrane potential and apoptosis induction. In the microscopic staining of cells, AA in the dosage close to the IC50 induced morphological changes typical for apoptosis. Taken together, these results demonstrate that AA has a pro-oxidative effect on Caco-2 cells, leading to apoptotic cell death.

2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

The present investigation was aimed to discover the activity of raw (RCNTs) and functionalized multi-walled carbon nanotubes (FCNTs) for their cytotoxic potential in human breast cancer (MCF-7) cells. The RCNTs were functionalized with the acid treatment method and were characterized by SEM and TEM. The morphology of RCNTs and FCNTs were found to be variable with a size range of ∼10–15 nm diameter were as the length goes up to 2–4 μm. For, cytotoxicity assessments, MCF-7 cells were exposed to RCNTs and FCNTs at 5–400 μg/ml concentrations for 24 h. The cytotoxicity was measured by MTT and NRU assays, and cellular morphology using phase contrast microscope. Further, intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were also studied. The results of MTT and NRU assays exhibited a concentration-dependent decrease in cell viability of MCF-7 cells. The RCNTs and FCNTs exposed cells were also found to alter the normal morphology of MCF-7 cells. Furthermore, the cells showed significant induction in ROS generation and reduction in MMP level. The results of this study, demonstrated that RCNTs and FCNTs has the potential to induce cytotoxicity in MCF-7 cells which could be mediated through the reactive oxygen species (ROS) generation. [ABSTRACT FROM AUTHOR]

Cancer is one of the life-threatening diseases and a leading cause of death worldwide. Herbal medicine has a potential of treating many diseases. Nigella sativa L. is a widely used plant in traditional systems of medicine. The cytotoxic potential of Nigella sativa seed oil (NSO) was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), neutral red uptake (NRU) assays and morphological alterations in HepG2, MCF-7, A-549 and HEK293 cell lines. Further, the influence of cytotoxic concentrations (50–250 μg/ml) of NSO on oxidative stress markers (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) and mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9, Bax, Bcl-2) were studied. The results exhibited significant decrease in the percentage cell viability of HepG2, MCF-7 and A-549 cells in a concentration-dependent manner. However, NSO showed higher cytotoxic response in HepG2 cells and less in HEK293 cells. Therefore, HepG2 cells were selected to further investigate the underlying mechanism(s) responsible for the cytotoxic response. NSO was found to induce oxidative stress in a concentration-dependent manner, which was indicated by induction of ROS and LPO along with decrease in reduction in GSH and MMP. Quantitative real-time PCR data showed that following the exposure of HepG2 cells to NSO, the level of mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9 and bax) was up-regulated whereas, anti-apoptotic gene bcl-2 was down-regulated. The results demonstrated that NSO induced cytotoxicity and apoptosis in HepG2 cells via ROS generation, which is likely mediated through the p53 pathway. [ABSTRACT FROM AUTHOR]

Background: Cancer is a major health problem and exploiting natural products have been one of the most successful methods to combat this disease. Verbesina encelioides is a notorious weed with various pharmacological properties. The aim of the present investigation was to screen the anticancer potential of V. encelioides extract against human lung cancer (A-549), breast cancer (MCF-7), and liver cancer (HepG2) cell lines. Methods: A-549, MCF-7, and HepG2 cells were exposed to various concentrations of (10-1000 µg/ml) of V. encelioides for 24 h. Further, cytotoxic concentrations (250, 500, and 1000 µg/ml) of V. encelioides induced oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage in HepG2 cells were studied. Results: The exposure of cells to 10-1000 µg/ml of extract for 24 h, revealed the concentrations 250-1000 µg/ml was cytotoxic against MCF-7 and HepG2 cells, but not against A-549 cells. Moreover, the extract showed higher decrease in the cell viability against HepG2 cells than MCF-7 cells. Therefore, HepG2 cells were selected for further studies viz. oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage. The results revealed differential anticancer activity of V. encelioides against A-549, MCF-7 and HepG2 cells. A significant induction of oxidative stress, ROS generation, and MMP levels was observed in HepG2 cells. The cell cycle analysis and comet assay showed that V. encelioides significantly induced G2/M arrests and DNA damage. Conclusion: These results indicate that V encelioides possess substantial cytotoxic potential and may warrant further investigation to develop potential anticancer agent. [ABSTRACT FROM AUTHOR]

ZnO NPs (zinc oxide nanoparticles) has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species) production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications. [ABSTRACT FROM AUTHOR]

2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent. [ABSTRACT FROM AUTHOR]

[Display omitted] Aloe perryi plant in the genus Aloe (family: Asphodelaceae), have been used in traditional medicine systems. Herein, we aimed to analyze the anticancer effects of A. perryi petroleum ether extract (APPeE) against human breast cancer (MDA-MB-231) and normal (HEK-293) cell lines. Further the biomarker stigmasterol, isolated from A. perryi extract was quantified by a densitometric high-performance thin layer chromatography (HPTLC) method. The cytotoxic potential of APPeE was measured by MTT assay, neutral red uptake (NRU) assay, and morphological identification. APPeE-induced a concentration dependent strong cytotoxic effects on MDA-MB-231 cells with an IC 50 value of 24.5 μg/ml in contrast to HEK-293 (IC 50 value of > 100 μg/ml). Similar results were obtained by NRU assay. Further cytotoxic concentrations of APPeE increased reactive oxygen species (ROS) production and activated caspase-3 and −9, leading to apoptosis in MDA-MB-231 cells. Additionally, a significant augment in the expression of p53, Bax, caspase-3 and −9 with a decline in Bcl-2 gene expression confirmed the involvement of apoptosis pathway in MDA-MB-231 cell death. In HPTLC analysis, the solvent system hexane: ethylacetate (8:2 v/v) furnished a sharp peak for stigmasterol (Rf = 0.19 ± 0.001). The low value of % relative standard deviation (RSD) (0.97–1.39) proposed the method is robust. The limit of detection (LOD) and limit of quantification (LOQ) were established as 13.82 and 41.89 ng, respectively. The stigmasterol in APPeE was quantified as 0.238% w/w of dried APPeE. Hence, this study concludes the promising anticancer effect of APPeE, which might be endorsed to the existence of known anticancer biomarker stigmasterol. [ABSTRACT FROM AUTHOR]