Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of beta-catenin.
Alterations in the Wnt/beta-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/beta-catenin pathway. Decursin antagonized beta-catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of beta-catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of beta-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 beta-catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/beta-catenin pathway.
Song
Gyu-Yong
GY
College of Pharmacy, Chungnam National University, Daejeon, Korea.
Lee
Jee-Hyun
JH
Cho
Munju
M
Park
Byeoung-Soo
BS
Kim
Dong-Eun
DE
Oh
Sangtaek
S
D000726:Androgen Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000728:Androgens / Q000502:physiology*; D029969:Angelica; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000726:Androgen Antagonists; D000728:Androgens; D001578:Benzopyrans; D002087:Butyrates; D010936:Plant Extracts; D051176:beta Catenin; C101278:decursin