Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells

• Published in: Cell biology international Vol. 33; no. 2; pp. 239 - 246
• Main Authors: Karabulut, B., Erten, C., Gul, M.K., Cengiz, E., Karaca, B., Kucukzeybek, Y., Gorumlu, G., Atmaca, H., Uzunoglu, S., Sanli, U.A., Baran, Y., Uslu, R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier Ltd 01.02.2009; Blackwell Publishing Ltd
• Subjects: Androgens - physiology; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Bcl-2; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell Line, Tumor; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; DNA Fragmentation - drug effects; Docetaxel; Down-Regulation; Drug Resistance, Neoplasm; Drug Synergism; DU-145; Humans; Imidazoles - pharmacology; Imidazoles - therapeutic use; Male; PC-3; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Taxoids - pharmacology; Taxoids - therapeutic use; Zoledronic acid; Bcl-2; Zoledronic acid; DU-145; PC-3; Prostate cancer; Docetaxel
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1016/j.cellbi.2008.11.011

Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.