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
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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).
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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doi:10.1124/mol.107.040253.
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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
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