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.
Department of Urology, Osaka City University, Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan. tomoaki826@msic.med.osaka-cu.ac.jp
Tomoaki
T
Tanaka
Hidenori
H
Kawashima
Keiko
K
Ohnishi
Kentaro
K
Matsumura
Rikio
R
Yoshimura
Masahide
M
Matsuyama
Katsuyuki
K
Kuratsukuri
Tatsuya
T
Nakatani
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