Document Detail

Bcl-2 overexpression sensitizes MCF-7 cells to genistein by multiple mechanisms.
MedLine Citation:
PMID:  17786319     Owner:  NLM     Status:  MEDLINE    
Genistein is a soy isoflavone with anti-tumor properties. Genistein-induced apoptosis involves Bcl-2 downregulation. However, overexpression of Bcl-2 in breast cancer has been associated with better prognosis and response to hormonal therapy. To examine genistein's effect on breast cancer cells with different Bcl-2 levels, we established control (MCF-7/PV) and Bcl-2 overexpressing MCF-7 (MCF-7/Bcl-2) cell lines and characterized genistein regulated apoptosis and cell cycle progression in these cells. Our results demonstrate that overexpression of Bcl-2 rendered MCF-7 cells more sensitive, rather than resistant, to genistein. We found that genistein induces enhanced cytochrome c release and mitochondrial membrane depolarization in MCF-7/Bcl-2 cells, as compared to control. We also found that genistein increases Bcl-2 levels and Bcl-2/Bax ratio in the mitochondrial fractions of MCF-7/Bcl-2 cells, suggesting that disturbed Bcl-2/Bax distribution may cause cytochrome c release and apoptosis in these cells. Cell cycle analysis indicated that genistein induces G0/G1 arrest in MCF-7/PV cells but increases in G2/M arrest in MCF-7/Bcl-2 cells. This was accompanied by modified responses of several cell cycle regulators, such as p21 and cyclin B1. Taken together, our results indicate that genistein-Bcl-2 interaction switches Bcl-2 from an anti-apoptotic protein into a proapoptotic protein, which involves disturbed Bcl-2/Bax distribution in mitochondria, increased cytochrome c release and modified cell cycle regulation.
Chaitali Tophkhane; Shihe Yang; Wesley Bales; Linda Archer; Adeboye Osunkoya; Ann D Thor; Xiaohe Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  31     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-05     Completed Date:  2007-11-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  867-74     Citation Subset:  IM    
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Breast Neoplasms / drug therapy*,  genetics,  pathology
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cytochromes c / metabolism
Flow Cytometry
Genistein / pharmacology*
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects
Proto-Oncogene Proteins c-bcl-2 / drug effects,  metabolism*
Tumor Cells, Cultured / drug effects
bcl-2-Associated X Protein / metabolism
Reg. No./Substance:
0/Antineoplastic Agents; 0/BAX protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 446-72-0/Genistein; 9007-43-6/Cytochromes c

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