Browsing by Subject "heat shock protein 27"
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Item Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells(2013) Karaca B.; Atmaca H.; Bozkurt E.; Kisim A.; Uzunoglu S.; Karabulut B.; Sezgin C.; Sanli U.A.; Uslu R.We investigated the effects of AT-101/cisplatin combination treatment on the expression levels of apoptotic proteins and epigenetic events such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzyme activities in OVCAR-3 and MDAH-2774 ovarian cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were performed. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. DNMT and HDAC activities were evaluated by ELISA assay and mRNA levels of DNMT1 and HDAC1 genes were quantified by qRT-PCR. Combination of AT-101/cisplatin resulted in strong synergistic cytotoxicity and apoptosis in human ovarian cancer cells. Combination treatment reduced some pivotal anti-apoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, XIAP in OVCAR-3 cells, whereas p21, Bcl-2, cIAP-1, HSP27, Clusterin and XIAP in MDAH-2774 cells. Among the pro-apoptotic proteins, Bad, Bax, Fas, phospho-p53 (S46), Cleaved caspase-3, SMAC/Diablo, TNFR1 and Cytochrome c were induced in OVCAR-3 cells, whereas, Bax, TRAILR2, FADD, p27, phospho-p53 (S46), Cleaved caspase-3, Cytochrome c, SMAC/Diablo and TNFR1 were induced in MDAH-2774 cells. Combination treatment also inhibited both DNMT and HDAC activities and also mRNA levels in both ovarian cancer cells. AT-101 exhibits great potential in sensitization of human ovarian cancer cells to cisplatin treatment in vitro, suggesting that the combination of AT-101 with cisplatin may hold great promise for development as a novel chemotherapeutic approach to overcome platinum-resistance in human ovarian cancer. © 2012 Springer Science+Business Media Dordrecht.Item Quercetin-mediated apoptosis and cellular senescence in human colon cancer(Bentham Science Publishers, 2020) Özsoy S.; Becer E.; Kabadayı H.; Vatansever H.S.; Yücecan S.Background: Quercetin is a flavonol from the flavonoid group of polyphenols, which positively affects human health due to its anti-cancer, anti-inflammatory, anti-microbial and cardioprotective effects. The effects of phenolic compounds, including quercetin, on programmed cell death and cellular senescence, have been the subject of research in recent years. Objective: In this study, we aimed to investigate the effects of quercetin on cell viability, apoptosis and cellular senescence in primary (Colo-320) and metastatic (Colo-741) colon adenocarcinoma cell lines. Methods: Cytotoxicity was analyzed via MTT assay in Colo-320 and Colo-741 cell lines. After quercetin treatment, cell ularsenescence and apoptosis were evaluated by TUNEL staining, X-Gal staining and indirect peroxidase tech-nique for immunocytochemical analysis of related proteins such as Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1. Results: The effective dose for inhibition of cell growth in both cell lines was determined to be 25µg/ml quercetin for 48 hours. Increased Baximmunoreactivityfollowingquercetin treatment was significant in both Colo-320 and Colo-741 cell lines, but decreased Bcl-2 immunoreactivitywas significant only in theColo-320 primary cell line. In addition, after quercetin administration, the number of TUNEL positive cells and, immunoreactivities for p16, Lamin B1 and cyclin B1 in both Colo-320 and Colo-741 cells increased. Conclusion: Our results suggest that quercetin may only induce apoptosis in primary colon cancer cells. Further-more, quercetin also triggered senescence in colon cancer cells, but some cells remained alive, suggesting that colon cancer cells might have escaped from senescence. © 2020 Bentham Science Publishers.Item Resveratrol triggers Apoptosis in colon cancer cells rather than senescence(Mattioli 1885, 2021) Madencioğlu S.; Becer E.; Kabadayı H.; Vatansever H.S.; Yücecan S.Objective: Resveratrol is a phenolic compound that classified in stilbenoid and used as anticancer agent in many cancer types. The purpose of the study is to determine apoptotic and senescence inducing effects in primary (Colo-320) and metastatic (Colo-741) colon cancer cells. Methods: Cell growth and cytotoxicity were detected by MTT method in both Colo-320 and Colo-741 cell lines. Apoptotic and senescence inducing activities were tested with TUNEL staining, X-gal staining and immunocytochemistry using antibodies directed against to Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1. Results: According to MTT results, 25 μg/mL and 10 μg/mL concentrations of resveratrol were found more effective for Colo-320 and Colo-741 cell lines, respectively. As a result of immunocytochemical staining, Bax immunoreactivity was significantly increased while Bcl-2 immunoreactivity significantly decreased in Colo-320 cell line. Increased Hsp27, lamin B1 and p16 immunoreactivities on Colo-320 cells were not significant. In Colo-741 cells, Bcl-2 immunoreactivity was significantly increased. Hsp27 immunoreactivity in Colo-320 cell line was significantly higher than Colo-741 cell line. In addition, after resveratrol administration, while the TUNEL positive cells significantly increased in Colo-320 cells, X-gal positive cells was detected in Colo-741 than Colo-320 cells. Conclusion: Resveratrol can inhibit cell viability both in primer and metastatic colon cancer cells. However, resveratrol might be more effective triggering mitochondrial-mediated apoptosis in primary colon cancer cells. Apoptotic and cell cycle inhibiting effects of resveratrol may differ by cell type. Therefore, resveratrol may be a potential phytotherapeutic agent for colon cancer according to the cell origin. © Mattioli 1885.