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A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells.
Cancer Res. 2005 Feb 01; 65(3):1035-44.CR

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 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.

Authors+Show Affiliations

Department of Pharmacy, Sahm Yook University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15705905

Citation

Yim, Dongsool, et al. "A Novel Anticancer Agent, Decursin, Induces G1 Arrest and Apoptosis in Human Prostate Carcinoma Cells." Cancer Research, vol. 65, no. 3, 2005, pp. 1035-44.
Yim D, Singh RP, Agarwal C, et al. A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Res. 2005;65(3):1035-44.
Yim, D., Singh, R. P., Agarwal, C., Lee, S., Chi, H., & Agarwal, R. (2005). A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Research, 65(3), 1035-44.
Yim D, et al. A Novel Anticancer Agent, Decursin, Induces G1 Arrest and Apoptosis in Human Prostate Carcinoma Cells. Cancer Res. 2005 Feb 1;65(3):1035-44. PubMed PMID: 15705905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. AU - Yim,Dongsool, AU - Singh,Rana P, AU - Agarwal,Chapla, AU - Lee,Sookyeon, AU - Chi,Hyungjoon, AU - Agarwal,Rajesh, PY - 2005/2/12/pubmed PY - 2005/3/15/medline PY - 2005/2/12/entrez SP - 1035 EP - 44 JF - Cancer research JO - Cancer Res VL - 65 IS - 3 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15705905/A_novel_anticancer_agent_decursin_induces_G1_arrest_and_apoptosis_in_human_prostate_carcinoma_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=15705905 DB - PRIME DP - Unbound Medicine ER -