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Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor alpha-negative breast cells

Title
Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor alpha-negative breast cells
Author
신인철
Keywords
Breast cancer; phytoestrogens; MCF-10A; MDA-MB-231; p53; p21
Issue Date
2011-02
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
NUTRITION RESEARCH, v. 31, NO 2, Page. 139-146
Abstract
In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-M B-231) estrogen receptor a (ER alpha) negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ER alpha-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ER alpha-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ER alpha-negative breast cancer. (C) 2011 Elsevier Inc. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0271531711000194?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffb
ISSN
0271-5317
DOI
10.1016/j.nutres.2011.01.011
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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