Differential effects of ibandronate, docetaxel and farnesol treatment alone and in combination on the growth of prostate cancer cell lines.
Ibandronate, one of the most potent bisphosphonates, has been shown to inhibit growth of various cancer cell lines. In contrast, little is known about the effects of ibandronate on prostate cancer cells. Therefore the aim of our study was to characterize the effects of ibandronate alone and in combination with docetaxel on the growth of prostate cancer cell lines and to identify the underlying signalling pathways. Material and methods. The prostate cancer cell lines LNCaP and PC-3 were treated with increasing concentrations of ibandronate and docetaxel alone and in combination. Viable cell number was measured after five days using a hemocytometer and the MTT-method. The effects of ibandronate were tentatively antagonized by addition of farnesyl-pyrophosphate (FPP) or farnesol (FOH). Results. Ibandronate inhibits growth of both prostate cancer cell lines in a dose dependent manner. In combination with docetaxel, synergistic effects are found as evidenced by a combination index (CI) of <1. Addition of FOH and FPP completely antagonized the growth inhibitory effects of ibandronate on both cell lines. Surprisingly, in combination with ibandronate and docetaxel, FOH further increased growth inhibition instead of antagonizing the growth inhibitory effects of ibandronate. Furthermore, FOH alone appeared to be a potent inhibitor of tumor cell growth. Discussion. Ibandronate effectively inhibits growth of prostate cancer cell lines via inhibition of the farnesyl-IPP-synthase and exhibits synergistic effects with docetaxel. In addition, FOH is a potent inhibitor of prostate cancer cell lines and may display an interesting treatment option for patients with CRPC.
Epplen
Robin
R
Division of Urologic Oncology, Department of Urology, University of Cologne, Cologne, Germany.
Stöckle
Michael
M
Engelmann
Udo
U
Heidenreich
Axel
A
Ohlmann
Carsten-Henning
CH
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival; D004164:Diphosphonates / Q000627:therapeutic use*; D000077143:Docetaxel; D004357:Drug Synergism; D005204:Farnesol / Q000627:therapeutic use*; D006801:Humans; D000077557:Ibandronic Acid; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D054876:Prenylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004164:Diphosphonates; D043823:Taxoids; D000077143:Docetaxel; D005204:Farnesol; D008798:Mevalonic Acid; D000077557:Ibandronic Acid