Emodin and aloe-emodin are the main bioactive components of anthraquinones found in Chinese herbal medicine, Rhubarb (Rheum palmatum), and aloe-emodin is also abundant in the leaves of aloe vera. Although emodin and aloe-emodin are capable of inhibiting cancer cell proliferation or inducing apoptosis, the recent studies suggest that the molecular targets of these two anthraquinones are different. Emodin has been reported to suppress HER-2-overexpressing breast cancer cells proliferation through decreasing HER-2 tyrosine kinase activity. Besides, emodin affected androgen receptor (AR) transcriptional activity by preventing AR nuclear translocation and promoted AR degradation. Aloe-emodin has been found the antiproliferative effects on breast cancer cells which is through estrogen receptor (ER)-modulating ability. Interestingly, emodin and aloe-emodin share similar structure with different functions by hitting different targets. Therefore, the molecular mechanisms of aloe-emodin causing cancer cell death are interesting to explore. Here, three cancer cell lines were used in our experiments: LNCaP, a human prostate cancer cell line with AR expression; two human breast cancer cell lines: MDA-MB-453 with high expressions of HER-2 and AR; MCF-7 with low expressions of HER-2 and AR. In which, MCF-7 cells contain high expression level of ERα. Cells were treated with emodin or aloe-emodin for different time intervals and proliferation was determined. The results indicated that emodin decreased the proliferation of LNCaP and MDA-MB-453 which express high AR protein; however, MCF-7 with low AR protein were relatively insensitive to emodin treatment. Oppositely, aloe-emodin decreased cell proliferation in ER-positive MCF-7 cells but had no effects on LNCaP and MDA-MB-453 cells. Furthermore, the morphology of MCF-7 was dramatically changed after aloe-emodin treatment and cell death was apparently observed. The protein levels of HER-2, phospho-HER-2, and ErbB3 were decreased after aloe- emodin treatment while ERK was unaffected. In addition, the protein levels of ERα were reduced by aloe-emodin in dose-dependent manner; however, AR protein seems unaffected. In conclusion, our findings indicate that aloe-emodin selectively attacks targets in cancer cells and had potentials to treat HER-2/ER-positive breast cancer in the future.

Citation Information: Clin Cancer Res 2010;16(14 Suppl):B46.