Indirect antitumor effects of bisphosphonates on prostatic LNCaP cells co-cultured with bone cells.
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.
Tanaka
Tomoaki
T
Department of Urology, Osaka City University, Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan. tomoaki826@msic.med.osaka-cu.ac.jp
Kawashima
Hidenori
H
Ohnishi
Keiko
K
Matsumura
Kentaro
K
Yoshimura
Rikio
R
Matsuyama
Masahide
M
Kuratsukuri
Katsuyuki
K
Nakatani
Tatsuya
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D012333:RNA, Messenger; D011944:Receptors, Androgen; D000077211:Zoledronic Acid; D008156:Luciferases; D000077268:Pamidronate