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 U.A.
dc.contributor.authorUslu R.
dc.date.accessioned2025-04-10T11:10:42Z
dc.date.available2025-04-10T11:10:42Z
dc.date.issued2015
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. © 2014, International Society of Oncology and BioMarkers (ISOBM).
dc.identifier.DOI-ID10.1007/s13277-014-2682-6
dc.identifier.urihttp://hdl.handle.net/20.500.14701/49296
dc.publisherKluwer Academic Publishers
dc.titleZoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines
dc.typeArticle

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