Augmentation of the Cytotoxicity of Ibandronate by Y-27632 in Prostate Cancer Cell Lines

ABSTRACT Background Bisphosphonates, which have been used for the treatment of the metastatic bone disease and malignant hypercalcemia due many cancers. These drugs also inhibit mevalonate pathway that results in the reduction of Ras prenylation, which eventually inhibits tumor growth. Rho/Rho kinase signaling has a fundamental role in cancer cell proliferation, migration and metastasis. In this study, we aimed to investigate the effects of y-27632 (a Rho-kinase inhibitor) and ibandronate (a bisphosphonate) and their combination on cell proliferation in prostate cell lines. Methods The adherent prostate cell line, PC-3, was grown in RPMI-1640 supplemented with 10% fetal bovine serum, 1% L-glutamine, 1% penicillin (10.000U/ml) and streptomycin (10.000 mg/ml) in a humidified atmosphere of 5% CO2 at 37 oC for confluency. The cells were seeded in the wells of E-plates (24,000 cells/well) that allowed a real-time-monitoring of the cell index reflected cell growth and proliferation (xCELLigence, Roche). The cell index was evaluated at the different points of time (post-treatment 12, 24, 36, 48, 60 and 72 h) in the groups of, y-27632, ibandronate, the combination of these drugs and time-course control. Results Both ibandronate alone (10-100 mM) and y-27632 alone (50-100 mM) markedly decreased cell index. But the combination of ibandronate with y-27632 (in differrent concentrations but especially in higher concentrations) resulted in potentiation of cytotoxicity in prostate cell line. Conclusions Rho kinase inhibitors, bisphosphonates and their combinations may be used for the treatment of prostate cancer in the future, according to the possible beneficial results of clinical trials. Disclosure All authors have declared no conflicts of interest.