Document Detail

Indirect antitumor effects of bisphosphonates on prostatic LNCaP cells co-cultured with bone cells.
MedLine Citation:
PMID:  19414350     Owner:  NLM     Status:  MEDLINE    
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.
Tomoaki Tanaka; Hidenori Kawashima; Keiko Ohnishi; Kentaro Matsumura; Rikio Yoshimura; Masahide Matsuyama; Katsuyuki Kuratsukuri; Tatsuya Nakatani
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-07-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1089-94     Citation Subset:  IM    
Department of Urology, Osaka City University, Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.
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MeSH Terms
Antineoplastic Agents / pharmacology
Bone Density Conservation Agents / pharmacology
Cell Proliferation / drug effects
Coculture Techniques
Diphosphonates / pharmacology*
Imidazoles / pharmacology*
Luciferases / metabolism
Osteoblasts / cytology
Osteoclasts / cytology
Prostatic Neoplasms / drug therapy*,  metabolism,  pathology
RNA, Messenger / genetics,  metabolism
Receptors, Androgen / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcriptional Activation
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Bone Density Conservation Agents; 0/Diphosphonates; 0/Imidazoles; 0/RNA, Messenger; 0/Receptors, Androgen; 118072-93-8/zoledronic acid; 40391-99-9/pamidronate; EC 1.13.12.-/Luciferases

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