Bcl-2 overexpression sensitizes MCF-7 cells to genistein by multiple mechanisms.
Int J Oncol
; 31(4): 867-74, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17786319
ABSTRACT
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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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Proteínas Proto-Oncogénicas c-bcl-2
/
Genisteína
/
Antineoplásicos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos