A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells

Cancer Res. 2005 Feb 1;65(3):1035-44.


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 micromol/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 < 0.001) in DU145 and LNCaP cells, and G(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 < 0.05-0.001) and cleaved caspase-9, caspase-3, and poly(ADP-ribose) polymerase; however, pretreatment with all-caspases inhibitor (z-VAD-fmk) only partially reversed decursin-induced apoptosis, suggesting the involvement of both caspase-dependent and caspase-independent pathways. These findings suggest the novel anticancer efficacy of decursin mediated via induction of cell cycle arrest and apoptosis selectively in human prostate carcinoma cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Benzopyrans / pharmacology*
  • Butyrates / pharmacology*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Caspases / metabolism
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Enzyme Activation / drug effects
  • Epithelial Cells / drug effects
  • G1 Phase / drug effects*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Nuclear Magnetic Resonance, Biomolecular
  • Prostate / cytology
  • Prostate / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Kinase Inhibitors / pharmacology
  • Up-Regulation / drug effects


  • Benzopyrans
  • Butyrates
  • CDKN1A protein, human
  • CDKN1B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinase Inhibitor p27
  • decursin
  • Cyclin-Dependent Kinases
  • Caspases