Abstract
Alterations in the Wnt/β-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/β-catenin pathway. Decursin antagonized β-catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of β-catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of β-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–OH, had no effect on CRT, the level of intracellular β-catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/β-catenin pathway.
Footnotes
-
This work was supported by the Korea Science and Engineering Foundation grant funded by the Korea government (Ministry of Science and Technology) (R01-2006-000-10617-0) and Regional Innovation Center grants from Traditional and Bio-Medical Research Center, Daejeon University (RRC-04722, 2006) by Industrial Technology Evaluation and Planning (ITEP).
-
Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
-
doi:10.1124/mol.107.040253.
-
ABBREVIATIONS: Fz, Frizzled; CRT, β-catenin response transcription; APC, adenomatous polyposis coli; GSK-3β, glycogen synthase kinase-3β; CM, conditioned medium; β-TrCP, β-transducin repeat-containing protein; HEK, human embryonic kidney; hFz-1, human Frizzled-1; RT-PCR, reverse transcription-polymerase chain reaction; DMSO, dimethyl sulfoxide; MG-132, N-benzyoloxycarbonyl (Z)-Leu-Leu-leucinal; TCF, T-cell factor; AR, androgen receptor.
- Received July 20, 2007.
- Accepted September 12, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
