Zoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines

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dc.contributor.authorVarol, U
dc.contributor.authorDegirmenci, M
dc.contributor.authorKaraca, B
dc.contributor.authorAtmaca, H
dc.contributor.authorKisim, A
dc.contributor.authorUzunoglu, S
dc.contributor.authorSezgin, C
dc.contributor.authorSanli, UA
dc.contributor.authorUslu, R
dc.date.accessioned2024-07-18T12:06:01Z
dc.date.available2024-07-18T12:06:01Z
dc.description.abstractOur aim was to investigate the possible synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and zoledronic acid (ZA), in PC-3 hormone-refractory prostate cancer cells (HRPC), as well as their docetaxel-resistant sublines. We established a docetaxel-resistant cell line (PC-3R) from PC-3 prostate cancer cells, by intermittent exposure to increasing concentrations of docetaxel in vitro. We then examined the effect of ZA and docetaxel on cell proliferation in both PC-3 and PC-3R prostate cancer cells. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 enzyme activity were measured to verify apoptosis. According to our results, docetaxel and ZA were found to be synergistically cytotoxic and apoptotic in both PC-3 and docetaxel-resistant PC-3R cells, in a dose- and time-dependent manner. Combined treatment with docetaxel and ZA synergistically inhibited PC-3 cell growth in vitro through an enhanced induction of cell death, compared with either agent alone; this result was also evident on PC-3R cells. Moreover, we have also demonstrated that apoptosis was induced in prostate cancer cells exposed to these drugs by a concentration-dependent increase in DNA fragmentation and caspase 3/7 enzyme activity. We concluded that ZA, either with docetaxel or not, might still exert some cytotoxicity even in docetaxel-resistant cells. From the clinical perspective, when the clinician decided to change the treatment in the post-docetaxel setting, continuing or combination with ZA may be an effective therapeutic approach for the treatment of HRPC patients.
dc.identifier.issn1010-4283
dc.identifier.other1423-0380
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/10143
dc.language.isoEnglish
dc.publisherSAGE PUBLICATIONS LTD
dc.subjectACQUIRED DRUG-RESISTANCE
dc.subjectBISPHOSPHONATES
dc.subjectCOMBINATION
dc.subjectDEPENDENCE
dc.subjectPROTEIN
dc.subjectGENES
dc.titleZoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines
dc.typeArticle

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