Galectin-9 (Gal-9), a member of animal lectins’ family, is implicated in the induction of apoptosis in various cancer cells. Here, we evaluated the anti-tumor effect of Gal-9 in OVCAR-3 ovarian cancer cells. The effect of the Gal-9 on cell viability was evaluated using MTT assays. Apoptosis was assessed using Annexin-V staining. The assessment of mitochondrial membrane potential (Δ Ψ m) was performed using a JC-1 probe. The activity of caspase-3 and caspase-6 were evaluated with colorimetric assay. The production of reactive oxygen species (ROS) was applied by fluorescent probe. The expression levels of Bax and Bcl-2 were assessed using western blotting. The result showed that Gal-9 inhibits cell viability. Flow cytometry analysis showed that Gal-9 induces apoptosis in ovarian cancer cells. Moreover, Gal-9 decreased Δ Ψ m and increased the generation of ROS and caspase-3 and caspase-6 activities in ovarian cancer cells. Moreover, Gal-9 induced expression of Bax as well as inhibited expression of Bcl-2. In conclusion, our results indicated that Gal-9 induced apoptosis in ovarian cancer cells through mitochondrial pathway.

Introduction: Over the centuries, the genus Euphorbia was known to be toxic to humans and animals. Recently, in a primary study significant suppressive activity against phytohemagglutinin activated T-cell proliferation has been reported from this plant. Therefore, this study was designed to evaluate the cytotoxic effects of different parts of E. kopetdaghi against cancer cell lines.Methods: Filtration and in vacuo concentration resulted in a green gum which was subjected on silica gel CC (hexane/Acetone, 0®50) to several fractions: F1-F8. The inhibitory effects of obtained fractions with 5, 50, and 500 μg/ml concentrations were evaluated on proliferation and viability of cancer cells (OVCAR and EJ-138) in 48 hours treatment. Finally, cell viability was determined at a wavelength of 570 by 3-4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide (MTT) method.Results: Based on studies of microscopic observation and viability testing, F1, F2, F4, F5, F6, and F7 showed significant cytotoxic effect at concentration of 50 and 500 mg/ml against EJ-138 and OVCAR-3 cell lines. These fractions inhibited growth of EJ-138 and OVCAR-3 cells in a concentration-dependent manner. Fraction of F8 induced tumor promotion significantly in EJ-138 and OVCAR-3 cells, respectively.Conclusion: Due to the inhibitory properties of E. kopetdaghi extract and its fractions on cancer cells of OVCAR3 and EJ-13, isolation, purification and identification of compounds presented in the fractions possessing cytotoxic effects are recommended which were the area of our future research.

Introduction: Little information is available about phytochemical and biological properties of Cousinia genus. In a primary study, seven Cousinia species including C. verbascifolia showed cytotoxic activity ranged between 18.4 ± 0.59 to 87.9 ± 0.58 mg/mL. To the best of our knowledge, no other biological studies have been conducted on this plant. Therefore, in this study the cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells was evaluated.Methods: Filtration and in vacuo concentration of methanol extract resulted in a green gum which was subjected on reverse column chromatography. Semi polar fraction (41.3 g) eluted with water: methanol (20: 80), was then subjected on a silica gel column chromatography using hexane/acetone and resulted in 11 fractions. Finally, cytotoxic activities against ovarian and colon cancer cells were determined at a wavelength of 570 nm by Matrix metalloproteinase protein (MTT) standard method.Results: None of the fractions showed highly cytotoxic activity. Based on NCI, fractions Fr.1, Fr.2, Fr.4, Fr.5, Fr.6, Fr.8 and Fr.10 showed moderately cytotoxicity with IC50 values ranged between 119 to 190 mg/mL against OVCAR-3 cells. Fractions Fr.1, Fr.2, Fr.6, Fr.7 and Fr.8 showed moderately cytotoxic activity ranged between 118 to 194 mg/mL against HT-29 cells. Fr.10 and Fr.11 showed no cytotoxic activity.Conclusion: Due to the inhibitory properties of extract and its fractions on cancer cells, identification of responsible compounds possessing cytotoxic effects for generating possible new approach in medicinal chemistry are recommended.

Background and purpose: Ovarian cancer is the deadliest gynecological cancer. Bromodomain and extra terminal domain (BET) proteins play major roles in the regulation of gene expression at the epigenetic level. Jun Qi (JQ1) is a potent inhibitor of BET proteins. Regarding the short half-life and poor pharmacokinetic profile, JQ1 was loaded into newly developed nano-carriers. Chitosan nanoparticles are one of the best and potential polymers in cancer treatment. The present study aimed to build chitosan-JQ1 nanoparticles (Ch-J-NPs), treat OVCAR-3 cells with Ch-J-NPs, and evaluate the effects of these nanoparticles on cell cycle and apoptosis-associated genes. Experimental approach: Ch-J-NPs were synthesized and characterized. The size and morphology of Ch-J-NPs were defined by DLS and FE-SEM techniques. OVCAR-3 cells were cultured and treated with Ch-J-NPs. Then, IC50 was measured using MTT assay. The groups were defined and cells were treated with IC50 concentration of Ch-J-NPs, for 48 h. Finally, cells in different groups were assessed for the expression of genes of interest using quantitative RT-PCR. Findings/Results: IC50 values for Ch-J-NPs were 5. 625 µg/mL. RT-PCR results demonstrated that the expression of genes associated with cell cycle activity (c-MYC, hTERT, CDK1, CDK4, and CDK6) was significantly decreased following treatment of cancer cells with Ch-J-NPs. Conversely, the expression of caspase-3, and caspase-9 significantly increased. BAX (pro-apoptotic) to BCL2 (anti-apoptotic) expression ratio, also increased significantly after treatment of cells with Ch-J-NPs. Conclusion and implications: Ch-J-NPs showed significant anti-cell cyclic and apoptotic effects on OVCAR-3 cells.

Background and purpose: Ovarian cancer is the deadliest cancer in women. The main challenge in the inhibition of ovarian cancer cells is chemo-resistance. Seeking to overcome this issue, several strategies have been suggested, including the administration of natural products. Grape seed extract (GSE) is a good source of polyphenols and its anticancer effects have been reported by many studies. In this study we aimed to evaluate the effects of GSE on OVCAR-3, a chemo-resistant ovarian cancer line. Experimental approach: OVCAR-3 cells were treated with GSE (71 μ g/mL) for 24 and 48 h. Cell viability and cell apoptosis were measured by MTT and flow cytometry. The real-time polymerase chain reaction was used to determine the expression of genes involved in the cell cycle (PTEN, DACT1, AKT, MTOR, GSK3B, C-MYC, CCND1, and CDK4) and apoptosis (BAX, BCl2, CASP3, 8 and 9). The expression of CASP3 protein was evaluated by the CASP3 assay. Findings / Results: The results showed that treatment of OVCAR-3 cells with GSE, increased the expression level of PTEN and DACT1 tumor suppressor genes, as well as apoptotic genes, CASP3, 8, and 9 (P < 0. 001). Also, the induction of tumor suppressor genes expression was associated with an increase in the expression of BAX/BCL2 gene ratio as pro-and anti-apoptotic genes. The expression of the genes involved in the cell cycle, CCND1 and CDK4, was inhibited (P < 0. 001). The results indicated that GSE induced cell apoptosis in a time-dependent manner (P < 0. 001). Also, the GSE treatment resulted in the CASP3 protein expression (P < 0. 001). Conclusion and implications: According to the results of this study, GSE may exert anti-tumorigenic effects on chemo-resistant OVCAR-3 ovarian cancer cells which might be mediated by the expression of tumor suppressor genes that interact with cell signaling pathways, cell cycle, and cell apoptosis. Hence, the consumption of GSE extract during chemotherapy may overcome part of chemo-resistance in ovarian cancer.

Background and objectives: Cancer is a major health problem in the world. The aim of this study was to extract the flowers of Allium austroiranicum used by Iranian people as a condiment or for its medicinal effects followed by bioassay guided fractionation of the extracts and fractions, using anti-proliferative effects against ovarian and cervical cancer cells. Methods: The air-dried flowers of Allium austroiranicum were extracted in a four-step extraction method, resulting hexan, chloroform, chloroform: methanol (9: 1), butanol and aqueous extracts. Anti-proliferative effects of the extracts were evaluated by MTT assay against OVCAR-3, HeLa, and HUVEC cell lines. The most potent cytotoxic extract was then subjected to fractionation by MPLC method on a RP-18 silicagel column. Finally, the cytotoxic effects of resulted fractions were analyzed again and the most potent cytotoxic fraction and its IC50 were determined. Results: Statistical analysis showed that butanol extract of A. austroiranicum showed the most potent cytotoxic effects against OVCAR-3, HeLa and HUVEC cell lines with IC50 values of 38± 2, 56± 1. 4, and 60± 3. 5 μ g/mL, respectively. On the other hand, for 7 fractions resulting from fractionation of the butanol extract, MTT assay results showed that 6th fraction (F) was the most cytotoxic fraction with IC50 of 2. 7± 0. 26 and 7. 5± 0. 5 μ g/mL for OVCAR-3 and HeLa cancer cell lines, respectively. Primary evaluation of the fraction by TLC and NMR analysis suggested the steroidal saponins as the main constituents. Conclusion: Allium austroiranicum showed significant cytotoxic effects against ovarian cancer cell line especially fractions assumed to contain steroidal saponins. The fraction constituents have the potential of being strong cytotoxic agents and the isolation and identification of compounds are suggested.

Introduction: Nowadays, the prevalence of nicotine abuse among women has increased dramatically. In the current study, we aimed to investigate the effect of nicotine exposure on breast MCF-7 and ovarian OVCAR-3 cell lines for assessing the toxicity of nicotine in the cells of these organs. Methods: The MCF-7 and OVCAR-3 cells were treated with increasing nicotine concentrations ranging from 0 (control), 10-11, 10-8 and 10-6 M for 24h. Effect of nicotine treatments on major antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), cellular levels of glutathione (GSH) and malondialdehyde (MDA) were monitored. Results: We showed that the CAT activity in MCF-7 cells increased only at 10-6 M dose of nicotine. The GPx and GR activity was decreased at 10-8 and 10-6 M of nicotine in MCF-7 cells, but in OVCAR-3 cells, this decrease was significant only at 10-6 M dose of nicotine. Reduced GSH decrease was statistically significant only at 10-8 and 10-6 M of nicotine in MCF-7 cells; otherwise, in OVCAR-3 cells, this decline was significant only at 10-6 M of nicotine. Nicotine at 10-8 and 10-6 M concentration caused a significant increase in MDA levels in MCF-7 cells. Conclusion: This study showed that breast MCF-7 cells are more vulnerable than ovarian OVCAR-3 cells against nicotine-induced oxidative toxicity.