@article{oai:kanazawa-u.repo.nii.ac.jp:00026709,
 author = {Asahi, Hideki and Mizokami, Atsushi and Miwa, Sotaro and Keller, Evan T. and Koshida, Kiyoshi and Namiki, Mikio},
 issue = {5},
 journal = {International Journal of Urology},
 month = {May},
 note = {Aim: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. Methods: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. Results: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. Conclusions: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells., 金沢大学医学部附属病院泌尿器科},
 pages = {593--600},
 title = {Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells},
 volume = {13},
 year = {2006}
}