A novel anticancer agent, decursin, induces G 1 arrest and apoptosis in human prostate carcinoma cells : Yim D, Singh RP, Agarwal C, Lee S, Chi H, Agarwal R, Department of Pharmacy, Sahm Yook University, Seoul, Korea

Abstract

We isolated a coumarin compound decursin (C 19 H 20 O 5 ; molecular weight 328) from Korean angelica ( Angelica gigas ) root and characterized it by spectroscopy. Here, for the first time, we observed that decursin (25–100 μmol/L) treatment for 24 to 96 hours strongly inhibits growth and induces death in human prostate carcinoma DU145, PC-3, and LNCaP cells. Furthermore, we observed that decursinol [where (CH 3 ) 2 -C=CH-COO- side chain of decursin is substituted with -OH] has much lower effects compared with decursin, suggesting a possible structure-activity relationship. Decursin-induced growth inhibition was associated with a strong G 1 arrest ( P 1 , S as well as G 2 -M arrests depending upon doses and treatment times in PC-3 cells. Comparatively, decursin was nontoxic to human prostate epithelial PWR-1E cells and showed only moderate growth inhibition and G 1 arrest. Consistent with G 1 arrest in DU145 cells, decursin strongly increased protein levels of Cip1/p21 but showed a moderate increase in Kip1/p27 with a decrease in cyclin-dependent kinases (CDK); CDK2, CDK4, CDK6, and cyclin D1, and inhibited CDK2, CDK4, CDK6, cyclin D1, and cyclin E kinase activity, and increased binding of CDK inhibitor (CDKI) with CDK. Decursin-caused cell death was associated with an increase in apoptosis ( P