| Bcl-2 overexpression sensitizes MCF-7 cells to genistein by multiple mechanisms. | |
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MedLine Citation:
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PMID: 17786319 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Chaitali Tophkhane; Shihe Yang; Wesley Bales; Linda Archer; Adeboye Osunkoya; Ann D Thor; Xiaohe Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 31 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-09-05 Completed Date: 2007-11-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 867-74 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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 Female Flow Cytometry Genistein / pharmacology* Humans 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 |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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