Tanaka T, Kawashima H, Ohnishi K, Matsumura K, Yoshimura R, Matsuyama M, Kuratsukuri K, Nakatani T
Indirect Antitumor Effects of Bisphosphonates on Prostatic LNCaP Cells Co-cultured with Bone Cells. [Journal Article]
Anticancer Res 2009 Apr; 29(4):1089-94.
Bisphosphonates are strong inhibitors of osteoclastic bone resorption in both benign and malignant bone diseases. The nitrogen-containing bisphosphonates (N-BPs) have strong cytotoxicity via inhibition of protein prenylation in the mevalonate pathway, and also demonstrate direct cytostatic and proapoptotic effects on prostate cancer cells. We confirmed the usefulness of a co-culture system comprised of prostatic LNCaP cells, ST2 cells (mouse-derived osteoblasts) and MLC-6 cells (mouse-derived osteoclasts) in vitro. N-BPs (pamidronate and zoledronic acid) inhibited both androgen receptor transactivation and tumor cell proliferation by suppressing the activities of both osteoclasts and osteoblasts with low-dose exposure. This indirect inhibition of prostate cancer cells via bone cells could be beneficial in treating prostate cancer patients with bone metastases.
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