Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells
Language: 
English
Abstract: 

Although tamoxifen (TAM) is used for the front-line treatment and prevention of estrogen receptor-positive (ER+) breast tumors, nearly 40% of estrogen-dependent breast tumors do not respond to TAM treatment. Moreover, the positive response is usually of short duration, and most tumors eventually develop TAM-resistance. Overexpression of HER2 gene is associated with TAM-resistance of breast tumor, and suppression of HER2 expression enhances the TAM activity. Soy isoflavone genistein has been shown to have anti-cancer activities and suppress expression of HER2 and ERalpha. The objective of this study was to test the hypothesis that genistein may sensitize the response of ER+ and HER2-overexpressing breast cancer cells to TAM treatment. The combination treatment of TAM and genistein inhibited the growth of ER+/HER2-overexpressing BT-474 human breast cancer cells in a synergistic manner in vitro. Determination of cellular markers indicated that this synergistic inhibitory effect might be contributed in part from combined effects on cell-cycle arrest at G(1) phase and on induction of apoptosis. Further determination of the molecular markers showed that TAM and genistein combination synergistically induced BT-474 cell apoptosis in part by synergistic downregulation of the expression of survivin, one of the apoptotic effectors, and downregulation of EGFR, HER2, and ERalpha expression. Our research may provide a novel approach for the prevention and/or treatment of TAM insensitive/resistant human breast cancer, and warrants further in vivo studies to verify the efficacy of genistein and TAM combination on the growth of ER+/HER2-overexpressing breast tumors and to elucidate the in vivo mechanisms of synergistic actions.

Author(s): 
Mai, Zhiming
Blackburn, George L.
Zhou, Jin-Rong
Item Type: 
Journal Article
Publication Title: 
Molecular Carcinogenesis
Journal Abbreviation: 
Mol. Carcinog.
Publication Date: 
Jul 2007
Publication Year: 
2007
Pages: 
534-542
Volume: 
46
Issue: 
7
ISSN: 
0899-1987
DOI: 
10.1002/mc.20300
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 17295235 PMCID: PMC2683254

Turabian/Chicago Citation

Zhiming Mai, George L. Blackburn and Jin-Rong Zhou. Jul 2007. "Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells." Molecular Carcinogenesis 46: 7: 534-542. 10.1002/mc.20300.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1002/mc.20300 | issn = 0899-1987 | volume = 46 | pages = 534-542 | last = Mai | first = Zhiming | coauthors = Blackburn, George L., Zhou, Jin-Rong | title = Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells | journal = Molecular Carcinogenesis | date = Jul 2007 | pmid = | pmc = }} </ref>