Browsing by Subject "tumor necrosis factor related apoptosis inducing ligand"
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Item Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levels(2012) Kisim A.; Atmaca H.; Cakar B.; Karabulut B.; Sezgin C.; Uzunoglu S.; Uslu R.; Karaca B.Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has been shown to induce extrinsic pathway of apoptosis in many types of cancer cells. AT-101, an (-)-enantiomer of gossypol, is a potent anticancer agent that is shown to be an inhibitor of Bcl-2/Bcl-XL. In this study, we searched whether pretreatment with either of these drugs would result in the enhancement of apoptosis through induction of death receptors and activation of mitochondrial pathways within breast cancer cells. Methods: Human breast cancer (MCF-7 and MDA-MB-231) and normal breast cells (MCF-10A) were treated with drugs alone/in combination/sequentially. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were done. ELISA and Western blot analysis were done to assess DR4 and DR5 protein levels. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Results: The sequential treatment of AT-101 followed by TRAIL resulted in significant synergistic cytotoxicity and apoptosis. Moreover, pretreatment of breast cancer cells with AT-101 and then with TRAIL caused enhancement of the expression levels of DR4 and DR5 in both cancer cell lines, suggesting that these cells were under strong apoptotic stimuli. Conclusions: These findings all together, strongly suggest that pretreatment with AT-101 enhances TRAIL-induced death-inducing signaling complex resulting in the engagement of the mitochondrial pathway to apoptosis in breast cancer cells. These promising, preliminary results make AT-101 and TRAIL a novel combination treatment candidate for breast cancer. © Springer-Verlag 2012.Item A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells(Elsevier Ireland Ltd, 2013) Atmaca H.; Bozkurt E.; Uzunoglu S.; Uslu R.; Karaca B.Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer. © 2013 Elsevier Ireland Ltd.Item Piperlongumine inhibits cell growth and enhances TRAIL-induced apoptosis in prostate cancer cells(Wolters Kluwer Medknow Publications, 2020) Kismali G.; Ceylan A.; Meral O.; Alpay M.; Kosova F.; Cakir D.U.; Yurdakok-Dikmen B.; Tascene N.; Sel T.Objective: To investigate whether piperlongumine can sensitize prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trigger apoptosis in prostate cells. Methods: Human prostate cancer cell lines PC3, LNCaP, and VCaP were cultured with piperlongumine and TRAIL. Then, cell proliferation, migration, caspase activation, apoptotic protein expressions, and death receptor expressions were measured. Results: Piperlongumine inhibited cell proliferation at low doses (<10 μM) alone and in combination with TRAIL (25 ng/mL), induced apoptosis, and suppressed cyclooxygenase activation. Additionally, piperlongumine induced expression of death receptors which potentiated TRAIL-induced apoptosis in cancer cells but did not affect decoy receptors. Piperlongumine also downregulated tumor cell-survival pathways, inhibited colony formation and migration of cancer cells alone or in combination with TRAIL. The combination of piperlongumine with TRAIL was found to be synergistic. Conclusions: Our findings indicate that piperlongumine can sensitize cancer cells to TRAIL through the upregulation of death receptors and can trigger apoptosis with the downregulation of anti-apoptotic proteins. © 2020 Asian Pacific Journal of Tropical Biomedicine Produced by Wolters Kluwer Medknow. All rights reserved.Item Profiling of apoptosis-associated proteins in human prostate cancer cells in response to Montivipera bulgardaghica albizona venom by protein array(Taylor and Francis Ltd., 2021) Ilhan S.; Çiçek K.; Tok C.V.; Atmaca H.Here we studied the possible cytotoxic and apoptotic effects of Anatolian endemic mountain viper, Montivipera bulgardaghica albizona (M.b. albizona) venom on human PC-3 and DU-145 prostate cancer cell lines. M.b. albizona venom induced cytotoxicity and apoptosis of both prostate cancer cells in a concentration-dependent manner. Protein array results revealed that the levels of major components of the mitochondrion-initiated and the extrinsic death receptor-mediated pathways were significantly changed in prostate cancer cells by venom treatment. These data suggest that one or more of the purified components of the M.b. albizona venom may serve as an appropriate therapeutic agent for prostate cancer. Further bioactivity guided studies are required for the identification of bioactive compounds of M.b. albizona venom. © 2020 Informa UK Limited, trading as Taylor & Francis Group.