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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 376123, 12 pages
http://dx.doi.org/10.1155/2013/376123
Research Article

Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ERα Inhibition

1Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan
2Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
3Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan
4Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
5Department of Surgery, Chang Bing Show Chwan Memorial Hospital, Changhua 50544, Taiwan
6Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung 43304, Taiwan
7Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
8Department of Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan
9Graduate Institute of Rehabilitation Science, China Medical University, Taichung 40402, Taiwan

Received 25 April 2013; Accepted 6 June 2013

Academic Editor: Gautam Sethi

Copyright © 2013 Pao-Hsuan Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines of evidence indicate that emodin and aloe-emodin have estrogenic activity as phytoestrogens. However, their effects on estrogen receptor α (ERα) activation and breast cancer cell growth remain controversial. The goal of this study is to investigate the effects and molecular mechanisms of emodin and aloe-emodin on breast cancer cell proliferation. Our results indicate that both emodin and aloe-emodin are capable of inhibiting breast cancer cell proliferation by downregulating ERα protein levels, thereby suppressing ERα transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ERα and increased ERα ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ERα dissociation and ERα ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ERα degradation. Although emodin might induce cytosolic ERα degradation, it primarily affected nuclear ERα distribution similar to the action of estrogen when protein degradation was blocked. In conclusion, our data demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell proliferation by targeting ERα protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future.