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Tumor Biology

, Volume 36, Issue 2, pp 779–786 | Cite as

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

  • Umut Varol
  • Mustafa Degirmenci
  • Burcak Karaca
  • Harika Atmaca
  • Asli Kisim
  • Selim Uzunoglu
  • Canfeza Sezgin
  • Ulus Ali Sanli
  • Ruchan Uslu
Research Article

Abstract

Our 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.

Keywords

Zoledronic acid Cytotoxicity Apoptosis Docetaxel resistance Prostate cancer 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Umut Varol
    • 1
  • Mustafa Degirmenci
    • 2
  • Burcak Karaca
    • 3
  • Harika Atmaca
    • 4
  • Asli Kisim
    • 4
  • Selim Uzunoglu
    • 4
  • Canfeza Sezgin
    • 3
  • Ulus Ali Sanli
    • 3
  • Ruchan Uslu
    • 3
  1. 1.Medical Oncology ClinicIzmir Katip Celebi University Ataturk Training and Research HospitalIzmirTurkey
  2. 2.Medical Oncology ClinicIzmir Tepecik Training and Research HospitalIzmirTurkey
  3. 3.Department of Internal Medicine, Division of Medical Oncology, Faculty of MedicineEge UniversityIzmirTurkey
  4. 4.Section of Molecular Biology, Department of Biology, Faculty of Science and ArtsCelal Bayar UniversityManisaTurkey

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