Cytostatic and apoptotic effects of bisphosphonates on prostate cancer cells.
BACKGROUND
Bisphosphonates are potent inhibitors of bone resorption frequently used for breast cancer and myeloma-induced bone disease. Zoledronic acid has been recently shown to also reduce skeletal morbidity from prostate cancer.


METHODS
We have investigated the biological effects of bisphosphonates on PC-3 cell survival (MTT assay and DNA content). We compared four bisphosphonates at doses ranging from 10(-6) to 10(-4) M: clodronate, pamidronate, ibandronate and zoledronic acid. We analyzed cell cycle phases and assessed apoptotic effects of bisphosphonates by three different methods.


RESULTS
Clodronate exhibited only a slight inhibitory effect on cell growth. In contrast, aminobisphosphonates markedly decreased cell growth in a time- and dose-dependent manner exerting cytostatic and apoptotic effects. The largest effects were observed after six days of exposure to 10(-4) M bisphosphonates. Cytostatic effects were observed with all three aminobisphosphonates whereas apoptotic effects were especially evident after zoledronic acid incubation.


CONCLUSIONS
Aminobisphosphonates, especially zoledronic acid, markedly inhibited PC-3 cancer cell growth, through a variable combination of cytostatic and apoptotic effects. This activity could potentially contribute to the beneficial effects of bisphosphonates in prostate cancer patients with bone metastases.
Dumon
Jean-Claude
JC
Laboratory of Endocrinology and Bone Diseases, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. lmetabos@ulb.ac.be
Journé
Fabrice
F
Kheddoumi
Naïma
N
Lagneaux
Laurence
L
Body
Jean-Jacques
JJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D002470:Cell Survival; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004164:Diphosphonates