Received for publication July 23, 2007.
Revised September 5, 2007.
Accepted for publication September 12, 2007.

Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of -catenin

Abstract

Alterations in the Wnt/-catenin pathway are associated with the development and progression of human prostate cancer. Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, inhibits the growth of androgen-independent human prostate cancer cells, but little is known about its mechanism of action. Using a cell-based screen, we found that decursin attenuates the Wnt/-catenin pathway. Decursin antagonized -catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of -catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of -catenin, and thus inhibited the growth of PC3 prostate cancer cells. In contrast, decursinol, in which the (CH₃)₂-C=CH-COO-side chain of decursin is replaced with a -OH, had no effect on CRT, the level of intracellular -catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/-catenin pathway.

Key words: Oncogenes, Transcription targets, Tumor suppressors