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Eur Urol. 2004 Apr;45(4):521-8; discussion 528-9.

Cytostatic and apoptotic effects of bisphosphonates on prostate cancer cells.

Author information

1
Laboratory of Endocrinology and Bone Diseases, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. lmetabos@ulb.ac.be

Abstract

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.

PMID:
15041119
DOI:
10.1016/j.eururo.2003.12.012
[Indexed for MEDLINE]

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