Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ERαInhibition

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