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Horm Metab Res 2012; 44(13): 943-948
DOI: 10.1055/s-0032-1321818
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Formononetin-induced Apoptosis by Activation of Ras/p38 Mitogen-activated Protein Kinase in Estrogen Receptor-positive Human Breast Cancer Cells

J. Chen
1   School of Basic Medical Sciences, Guilin Medical University, Guangxi, Guilin, China
,
L. Sun
2   Department of Histology & Embryology, Guilin Medical University, Guangxi, Guilin, China
› Author Affiliations
Further Information

Publication History

received 30 April 2012

accepted 20 June 2012

Publication Date:
24 July 2012 (online)

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Abstract

Formononetin is one of the main active components of red clover plants, and considered as a phytoestrogen. Its pharmacological effects in vivo may be either estrogenic or anti-estrogenic, mainly depending upon the estrogen levels. Our recent studies suggested that formononetin inactivated IGF1/IGF1R-PI3K/Akt pathways and decreased cyclin D1 mRNA and protein expression in human breast cancer cells in vitro and in vivo. In the present study, we further investigated the molecular mechanisms involved in the induced apoptosis effect of formononetin on breast cancer cells. Our results suggested that formononetin inhibited the proliferation of ER-positive MCF-7 cells and T47D cells. In contrast, formononetin could not inhibit the cell of growth of ER-negative breast cancer cells such as MDA-MB-435 S cells. We further found that formononetin activated MAPK signaling pathway in a dose-dependent manner, which resulted in the increased ratio of Bax/Bcl-2, and induced apoptosis on MCF-7 cells. However, when MCF-7 cells were pretreated with p38MAPK inhibitor SB203580 before formononetin, apoptosis induced by formononetin was significantly attenuated. Thus, we conclude that the induced apoptosis effect of formononetin on human breast cancer cells were related to Ras-p38MAPK pathway. Considering that red clover plants are widely used clinically, our results provide the foundation for future development of formononetin for treatment of ER-positive breast cancer.

Key words

formononetin - breast cancer - MAPK - p38 - apoptosis
 

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