Inhibitory Effects of Bisphosphonates on the Proliferation of Human Ovarian Cancer Cell Lines and the Mechanism

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis and corticosteroid-induced bone loss. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due to direct antitumor effect. However, the effect of bisphosphonates to ovarian and endometrial cancers has not been elucidated. Thus, we examined the direct effect of bisphosphonates on the various ovarian cancer cell lines. Except for etidronate, all of bisphosphonates examined had the direct inhibitory effects on proliferation of all ovarian cancer cell lines used. Especially, pamidronate had the most marked inhibitory effect and inhibited dose-dependently the proliferation of ovarian cancer cell lines. KFr 13 cells among ovarian cancer cell lines used was the most sensitive to pamidronate and the caspase 3 activity was markedly stimulated by treatment with pamidronate, suggesting induction of apoptosis.