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Horm Metab Res 2012; 44(04): 263-267
DOI: 10.1055/s-0032-1301922
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Formononetin-induced Apoptosis of Human Prostate Cancer Cells Through ERK1/2 Mitogen-activated Protein Kinase Inactivation

Y. Ye
1   Department of Emergency, First Affiliated Hospital of Guangxi Medical University, Nanning, China
,
R. Hou
2   Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, China
,
J. Chen
3   Department of physiology, Guilin Medical University, Guilin, China
,
L. Mo
4   Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Nanning, China
,
J. Zhang
1   Department of Emergency, First Affiliated Hospital of Guangxi Medical University, Nanning, China
,
Y. Huang
5   Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning, Nanning, China
,
Z. Mo
4   Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Nanning, China
› Author Affiliations
Further Information

Publication History

received 05 December 2011

accepted 18 January 2012

Publication Date:
10 February 2012 (online)

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Abstract

Formononetin is a main active component of red clover plants (Trifolium pratense L.), and is considered as a phytoestrogen. Our previous studies demonstrated that formononetin caused cell cycle arrest at the G0/G1 phase by inactivating insulin-like growth factor 1(IGF1)/IGF1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in MCF-7 cells. In the present study, we investigated the molecular mechanisms involved in the effect of formononetin on prostate cancer cells. Our results suggested that higher concentrations of formononetin inhibited the proliferation of prostate cancer cells (LNCaP and PC-3), while the most striking effect was observed in LNCaP cells. We further found that formononetin inactivated extracellular signal-regulated kinase1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner, which resulted in increased the expression levels of BCL2-associated X (Bax) mRNA and protein, and induced apoptosis in LNCaP cells. Thus, we concluded that the induced apoptosis effect of formononetin on human prostate cancer cells was related to ERK1/2 MAPK-Bax pathway. Considering that red clover plants were widely used clinically, our results provided the foundation for future development of different concentrations formononetin for treatment of prostate cancer.

Key words

formononetin - phytoestrogen - IGF-1R - prostate cancer - ERK1/2
 

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