title: Incadronate induces cell detachment and apoptosis in prostatic PC-3 cells.
abstract: 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.
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, Gifu 502-8585, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iguchi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Usui
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirano
mesh_terms: 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
chemical_list: 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