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Inhibition of caveolin-1 expression by incadronate in PC-3 prostate cells
Kazuhiro Iguchi1, Shinji Matsunaga, Toru Nakano
1Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 502-8585, Japan. hirano@gifu-pu.ac.jp
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.
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