Inhibition of Caveolin-1 Expression by Incadronate in PC-3 Prostate Cells

Abstract

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. Materials and 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. Conclusion: These results indicate that the decrease in caveolin-1 expression elicited by incadronate is related to the inhibition of protein geranylgeranylation.