Incadronate induces cell detachment and apoptosis in prostatic PC-3 cells.
BACKGROUND
Bisphosphonates are widely used for the treatment and prevention of osteoporosis and are also effective in the treatment of bone metastasis of prostate cancer. Several mechanisms underlying the antitumor effect of bisphosphonates have been proposed, including direct effects on tumor cells, such as induction of apoptosis and inhibition of invasion.


METHODS
The detached and adherent cells after incadronate treatment were collected separately and stained with trypan blue solution.


RESULTS
It was found that incadronate induced cell detachment with dephosphorylation of focal adhesion kinase (FAK). The induction of cell detachment by incadronate was prevented by coincubation with geranylgeraniol. The activation of caspase-3 was observed in incadronate-treated floating cells, but not in the adherent cells. A caspase inhibitor did not inhibit cell detachment by incadronate but it markedly prevented cell death.


CONCLUSIONS
These results suggest that incadronate induces cell detachment, followed by caspase-dependent apoptosis.
Matsunaga
Shinji
S
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, Gifu 502-8585, Japan.
Iguchi
Kazuhiro
K
Usui
Shigeyuki
S
Hirano
Kazuyuki
K
D017209:Apoptosis / Q000187:drug effects*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D061945:Caspase Inhibitors; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology
D061945:Caspase Inhibitors; D004164:Diphosphonates; D011480:Protease Inhibitors; C093260:benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene; C071542:cimadronate; D001224:Aspartic Acid; D005047:Etoposide; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008798:Mevalonic Acid