Document Detail


Xanthorrhizol, a natural sesquiterpenoid, induces apoptosis and growth arrest in HCT116 human colon cancer cells.
MedLine Citation:
PMID:  19926935     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Xanthorrhizol is a sesquiterpenoid from the rhizome of Curcuma xanthorrhiza. In our previous studies, xanthorrhizol suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, inhibited cancer cell growth, and exerted an anti-metastatic effect in an animal model. However, the exact mechanisms for its inhibitory effects against cancer cell growth have not yet been fully elucidated. In the present study, we investigated the growth inhibitory effect of xanthorrhizol on cancer cells. Xanthorrhizol dose-dependently exerted antiproliferative effects against HCT116 human colon cancer cells. Xanthorrhizol also arrested cell cycle progression in the G0/G1 and G2/M phase and induced the increase of sub-G1 peaks. Cell cycle arrest was highly correlated with the downregulation of cyclin A, cyclin B1, and cyclin D1; cyclin-dependent kinase 1 (CDK1), CDK2, and CDK4; proliferating cell nuclear antigen; and inductions of p21 and p27, cyclin-dependent kinase inhibitors. The apoptosis by xanthorrhizol was markedly evidenced by induction of DNA fragmentation, release of cytochrome c, activation of caspases, and cleavage of poly-(ADP-ribose) polymerase. In addition, xanthorrhizol increased the expression and promoter activity of pro-apoptotic non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). These findings provide one plausible mechanism for the growth inhibitory activity of xanthorrhizol against cancer cells.
Authors:
You-Jin Kang; Kwang-Kyun Park; Won-Yoon Chung; Jae-Kwan Hwang; Sang Kook Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  111     ISSN:  1347-8648     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-20     Completed Date:  2010-02-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  276-84     Citation Subset:  IM    
Affiliation:
College of Pharmacy, Ewha Womans University, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / biosynthesis,  genetics
Blotting, Western
Cell Cycle / drug effects
Cell Cycle Proteins / biosynthesis,  genetics
Cell Division / drug effects
Cell Proliferation / drug effects
Cyclin-Dependent Kinases / metabolism
DNA Fragmentation
Flow Cytometry
Genes, Reporter
Growth Differentiation Factor 15 / metabolism
HCT116 Cells
Humans
Indicators and Reagents
Phenols / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Apoptosis Regulatory Proteins; 0/Cell Cycle Proteins; 0/GDF15 protein, human; 0/Growth Differentiation Factor 15; 0/Indicators and Reagents; 0/Phenols; 0/xanthorrhizol; EC 2.7.11.22/Cyclin-Dependent Kinases

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