Document Detail


Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway.
MedLine Citation:
PMID:  18761399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genistein, an isoflavonoid present in soybeans, exhibits anti-carcinogenic effects. Several studies have shown that genistein inhibits cell proliferation and triggers apoptosis in human breast cancer cells. In this study, we assessed the role of the MEK-ERK cascade in the regulation of genistein-mediated cell apoptosis in MDA-MB-231 cells. The results indicate that genistein, in a concentration-dependent manner, suppresses the protein levels of MEK5, total ERK5, and phospho-ERK5, effects that are consistent with inhibition of cell growth and induction of apoptosis. Exposure of these cells to genistein results in a concentration-dependent decrease in NF-kappaB/p65 protein levels and DNA-binding activity of NF-kappaB. Genistein down-regulates Bcl-2 and up-regulates Bax. NF-kappaB binding sites are present in the promoter of Bcl-2, suggesting that genistein might inhibit the expression of Bcl-2 through down-regulation of NF-kappaB. Exposure of MDA-MB-231 cells to genistein results in cleavage of caspase-3 and induction of caspase-3 activity in a concentration-dependent manner. Genistein inhibits NF-kappaB activity via the MEK5/ERK5 pathway; it also inhibits cell growth and induces apoptosis. In conclusion, inhibition of the MEK5/ERK5/NF-kappaB pathway may be an important mechanism by which genistein suppresses cell growth and induces apoptosis.
Authors:
Zhong Li; Jing Li; Baoqing Mo; Chunyan Hu; Huaqing Liu; Hong Qi; Xinru Wang; Jida Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-12
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  22     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-22     Completed Date:  2008-12-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1749-53     Citation Subset:  IM    
Affiliation:
The Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of Toxicology, Nanjing Medical University, No. 140 Hanzhong Road, Jiangsu, Nanjing 210029, China. uiuclz@126.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Breast Neoplasms / drug therapy*,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Female
Gene Expression Regulation, Neoplastic / drug effects
Genistein / administration & dosage,  isolation & purification,  pharmacology*
Humans
MAP Kinase Kinase 5 / drug effects,  metabolism
Mitogen-Activated Protein Kinase 7 / drug effects,  metabolism
Mitogen-Activated Protein Kinases / drug effects*,  metabolism
NF-kappa B / drug effects,  metabolism
Soybeans / chemistry
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/NF-kappa B; 446-72-0/Genistein; EC 2.7.11.24/Mitogen-Activated Protein Kinase 7; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 5

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


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