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.accessioned2024-07-22T08:14:02Z
dc.date.available2024-07-22T08:14:02Z
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.issn10104283
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16471
dc.language.isoEnglish
dc.publisherKluwer Academic Publishers
dc.subjectApoptosis
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectDiphosphonates
dc.subjectDrug Resistance, Neoplasm
dc.subjectDrug Synergism
dc.subjectHumans
dc.subjectImidazoles
dc.subjectMale
dc.subjectNeoplasms, Hormone-Dependent
dc.subjectProstatic Neoplasms
dc.subjectTaxoids
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectdocetaxel
dc.subjectzoledronic acid
dc.subjectbisphosphonic acid derivative
dc.subjectdocetaxel
dc.subjectimidazole derivative
dc.subjecttaxoid
dc.subjectzoledronic acid
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer cell
dc.subjectcancer resistance
dc.subjectcastration resistant prostate cancer
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectDNA fragmentation
dc.subjectdrug effect
dc.subjectdrug potentiation
dc.subjectenzyme activity
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectmale
dc.subjectpriority journal
dc.subjectapoptosis
dc.subjectdrug effects
dc.subjectdrug resistance
dc.subjectgenetics
dc.subjectNeoplasms, Hormone-Dependent
dc.subjectpathology
dc.subjectProstatic Neoplasms
dc.subjecttumor cell line
dc.titleZoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines
dc.typeArticle

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