Document Detail

Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells.
MedLine Citation:
PMID:  19536869     Owner:  NLM     Status:  MEDLINE    
This study is the first to investigate the anticancer effect of isoliquiritigenin (ISL) in human cervical carcinoma HeLa cells. The results reveal that ISL inhibits HeLa cells by blocking cell cycle progression in the G2/M phase and inducing apoptosis. Blockade of cell cycle is associated with increased activation of ataxia telangiectasia-mutated (ATM). Activation of ATM by ISL phosphorylated p53 at Serine15, resulting in increased stability of p53 by decreasing p53 and murine double minute-2 (MDM2) interaction. In addition, ISL-mediated G2/M phase arrest was also associated with decreases in the amounts of cyclin B, cyclin A, cdc2, and cdc25C, and increases in the phosphorylation of Chk2, cdc25C, and cdc2. The specific ATM inhibitor caffeine significantly decreased ISL-mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. ISL induced apoptotic cell death is associated with changes in the expression of Bax and Bak, decreasing levels of Bcl-2 and Bcl-X(L), and subsequently triggering mitochondrial apoptotic pathway. In addition, pretreatment of cells with caspase-9 inhibitor blocked ISL-induced apoptosis, indicating that caspase-9 activation is involved in ISL-mediated HeLa cell apoptosis. These findings suggest that ISL may be a promising chemopreventive agent against human uterine cervical cancer.
Ya-Ling Hsu; Chun-Chieh Chia; Ping-Jye Chen; Su-Er Huang; Soon-Cen Huang; Po-Lin Kuo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  53     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-08-17     Completed Date:  2009-10-22     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  826-35     Citation Subset:  IM    
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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MeSH Terms
Apoptosis / drug effects*
Cell Cycle / drug effects*
Cell Cycle Proteins / physiology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Chalcones / pharmacology*
DNA-Binding Proteins / physiology*
Glycyrrhiza / chemistry*
Hela Cells
Mitochondria / drug effects*
Protein-Serine-Threonine Kinases / physiology*
Proto-Oncogene Proteins c-mdm2 / physiology
Shallots / chemistry*
Tumor Suppressor Protein p53 / physiology*
Tumor Suppressor Proteins / physiology*
cdc25 Phosphatases / metabolism
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Chalcones; 0/DNA-Binding Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 961-29-5/isoliquiritigenin; EC Kinases; EC telangiectasia mutated protein; EC protein, human; EC Phosphatases; EC protein, human; EC Proteins c-mdm2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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