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Molecular Pharmacology

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Research ArticleArticle

Decursin Suppresses Human Androgen-Independent PC3 Prostate Cancer Cell Proliferation by Promoting the Degradation of β-Catenin

Gyu-Yong Song, Jee-Hyun Lee, Munju Cho, Byeoung-Soo Park, Dong-Eun Kim and Sangtaek Oh
Molecular Pharmacology December 2007, 72 (6) 1599-1606; DOI: https://doi.org/10.1124/mol.107.040253
Gyu-Yong Song
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Jee-Hyun Lee
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Munju Cho
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Byeoung-Soo Park
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Dong-Eun Kim
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Sangtaek Oh
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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
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Molecular Pharmacology: 72 (6)
Molecular Pharmacology
Vol. 72, Issue 6
1 Dec 2007
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Research ArticleArticle

Decursin Suppresses Human Androgen-Independent PC3 Prostate Cancer Cell Proliferation by Promoting the Degradation of β-Catenin

Gyu-Yong Song, Jee-Hyun Lee, Munju Cho, Byeoung-Soo Park, Dong-Eun Kim and Sangtaek Oh
Molecular Pharmacology December 1, 2007, 72 (6) 1599-1606; DOI: https://doi.org/10.1124/mol.107.040253

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Research ArticleArticle

Decursin Suppresses Human Androgen-Independent PC3 Prostate Cancer Cell Proliferation by Promoting the Degradation of β-Catenin

Gyu-Yong Song, Jee-Hyun Lee, Munju Cho, Byeoung-Soo Park, Dong-Eun Kim and Sangtaek Oh
Molecular Pharmacology December 1, 2007, 72 (6) 1599-1606; DOI: https://doi.org/10.1124/mol.107.040253
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