Inhibition of caveolin-1 expression by incadronate in PC-3 prostate cells.
BACKGROUND
Caveolin-1 is an essential component of caveolae and its expression is known to be increased in human prostate cancer. The reduction of caveolin-1 expression has been reported to decrease the tumorigenic and metastatic potential of prostate cancer.


METHODS
Caveolin-1 expression was determined by real-time RT-PCR and Western blot analysis.


RESULTS
Incadronate, a third-generation bisphosphonate, was found to inhibit the caveolin-1 mRNA and protein expression in PC-3 prostate cells. The decrease in caveolin-1 mRNA expression by incadronate was prevented by co-incubation with geranylgeranyol, but not with farnesol. Moreover, treatment of GGTI-286, a geranylgeranyl transferase inhibitor, but not FTI-277, a farnesyl transferase inhibitor, also resulted in the inhibition of caveolin-1 mRNA expression.


CONCLUSIONS
These results indicate that the decrease in caveolin-1 expression elicited by incadronate is related to the inhibition of protein geranylgeranylation.
Iguchi
Kazuhiro
K
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 502-8585, Japan. hirano@gifu-pu.ac.jp
Matsunaga
Shinji
S
Nakano
Toru
T
Usui
Shigeyuki
S
Hirano
Kazuyuki
K
D051242:Caveolin 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013729:Terpenes / Q000378:metabolism
C495540:CAV1 protein, human; D051242:Caveolin 1; D004164:Diphosphonates; D012333:RNA, Messenger; D013729:Terpenes; C071542:cimadronate