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

摘要

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 a (ERa) 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 ERa protein levels, thereby suppressing ERa transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ERa and increased ERa ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ERa dissociation and ERa ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ERa degradation. Although emodin might induce cytosolic ERa degradation, it primarily affected nuclear ERa 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 ERa protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future.