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dc.contributor.authorKütük, Özgür
dc.contributor.authorArısan, Elif Damla
dc.contributor.authorTezil, Tuğsan
dc.contributor.authorShoshan, Maria C.
dc.contributor.authorBaşağa, Hüveyda
dc.date.accessioned2019-02-07T13:19:18Z
dc.date.available2019-02-07T13:19:18Z
dc.date.issued2009-09-01
dc.identifier.issn0143-3334
dc.identifier.other1460-2180
dc.identifier.urihttps://doi.org/10.1093/carcin/bgp165
dc.identifier.urihttps://hdl.handle.net/11413/4487
dc.description.abstractIncreased expression of antiapoptotic Bcl-2 proteins confers therapeutic resistance in various cancer types. Targeting Bcl-2 proteins by small molecules or activating alternative pathways to bypass Bcl-2-mediated protection to promote apoptosis are two approaches to overcoming therapeutic resistance. Here, we show that cisplatin triggers a Bak-dependent pathway to induce apoptosis in Bcl-2-overexpressing MCF-7 cells. p53-mediated induction of Noxa expression, generation of lipid peroxidation end products and induction of Noxa–Mcl-1 interaction are necessary for this pathway to function. Although Puma is also induced by cisplatin treatment, it is not required for apoptosis. Similarly, reactive oxygen species production by cisplatin did not have any effect on cisplatin-induced apoptosis in MCF-7 Bcl-2 cells. Furthermore, p53 promotes cisplatin-induced apoptosis by directly binding and counteracting Bcl-x L antiapoptotic function. In conclusion, our findings suggest a novel mode of action for cisplatin to overcome Bcl-2-mediated protection against apoptosis, which requires preferential activation of Bak and p53-mediated upregulation of Noxa protein levels and lipid peroxidation.tr_TR
dc.language.isoen_UStr_TR
dc.publisherOxford University Presstr_TR
dc.relationCarcinogenesistr_TR
dc.subjectINDUCED CELL-DEATHtr_TR
dc.subjectOXIDATIVE STRESStr_TR
dc.subjectCANCER-CELLStr_TR
dc.subjectMITOCHONDRIAL APOPTOSIStr_TR
dc.subjectBH3-ONLY PROTEINStr_TR
dc.subjectHYDROGEN-PEROXIDEtr_TR
dc.subjectIN-VIVOtr_TR
dc.subjectBCL-2tr_TR
dc.subjectP53tr_TR
dc.subjectACTIVATIONtr_TR
dc.subjectapoptosistr_TR
dc.subjectcisplatintr_TR
dc.subjectbcl2 genetr_TR
dc.subjectlipid peroxidationtr_TR
dc.subjectmcf-7 cellstr_TR
dc.subjectCancer Biologytr_TR
dc.titleCisplatin overcomes Bcl-2-mediated resistance to apoptosis via preferential engagement of Bak: critical role of Noxa-mediated lipid peroxidationtr_TR
dc.typeArticletr_TR
dc.contributor.authorID123510tr_TR
dc.contributor.authorID113920tr_TR


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