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Decursin inhibits growth of human bladder and colon cancer cells via apoptosis, G1-phase cell cycle arrest and extracellular signal-regulated kinase activation

Authors
 Wun-Jae Kim  ;  Se-Jung Lee  ;  Young Deuk Choi  ;  Sung-Kwon Moon 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Vol.25(4) : 635-641, 2010 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
ISSN
 1107-3756 
Issue Date
2010
MeSH
Apoptosis/drug effects* ; Benzopyrans/pharmacology* ; Butyrates/pharmacology* ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colonic Neoplasms/enzymology* ; Colonic Neoplasms/pathology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cytochromes c/metabolism ; Down-Regulation/drug effects ; Drug Screening Assays, Antitumor ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; G1 Phase/drug effects* ; Humans ; MAP Kinase Kinase 1/antagonists & inhibitors ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/antagonists & inhibitors ; MAP Kinase Kinase 2/metabolism ; Protein Kinase Inhibitors/pharmacology ; Up-Regulation/drug effects ; Urinary Bladder Neoplasms/enzymology* ; Urinary Bladder Neoplasms/pathology* ; bcl-2-Associated X Protein/metabolism
Keywords
decursin ; bladder cancer cells ; colon cancer cells ; G1-phase cell cycle arrest ; apoptosis ; p21WAF1 ; extracellular signalregulated kinases
Abstract
Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, has demonstrated anti-cancer properties. In the present study, we found that decursin inhibited cell viability in cultured human urinary bladder cancer 235J cells and colon cancer HCT116 cells. The inhibited proliferation was due to apoptotic induction, because both cells treated with decursin dose-dependently showed a sub-G1 phase accumulation and an increased cytoplasmic DNA-histone complex. Cell death caused by decursin was also associated with the down-regulation of anti-apoptotic factor Bcl-2 and the up-regulation of pro-apoptotic molecules cytochrome c, caspase 3 and Bax. Treatment of both types of cancer cells with decursin resulted in G1-phase cell cycle arrest, as revealed by FACS analyses. In addition, decursin increased protein levels of p21WAF1 with a decrease in cyclins and cyclin dependent kinases (CDKs). Furthermore, decursin induced the activation of extracellular signal-regulated kinases (ERK) in both cancer cell lines, with the notable exceptions of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase. Finally, pretreatment with ERK-specific inhibitor PD98059 reversed decursin-induced p21WAF1 expression and decursin-inhibited cell growth. Thus, these findings suggest that decursin has potential therapeutic efficacy for the treatment of bladder and colon cancer.
Full Text
http://www.spandidos-publications.com/ijmm/25/4/635?text=abstract
DOI
10.3892/ijmm_00000386
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Choi, Young Deuk(최영득) ORCID logo https://orcid.org/0000-0002-8545-5797
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100694
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