Furanodienone Inhibits Cell Proliferation and Survival by Suppressing ER alpha Signaling in Human Breast Cancer MCF-7 Cells

Estrogen receptor alpha (ER alpha) plays an important role in the development and progression of breast cancer and thus the attenuation of ER alpha activities is a promising treatment strategy. Furanodienone is one of the main bioactive chemical components of Rhizoma Curcumae which is commonly used in Chinese medicine for the treatment of cancer. In this study, we investigated the effects of furanodienone on human breast cancer MCF-7, T47D, and MDA-MB-231 cells. Our results showed that furanodienone could inhibit MCF-7, T47D, and MDA-MB-231 cells proliferation in a dose (10-160 mu M) dependent manner. ER alpha-negative MDA-MB-231 cells were less sensitive to furanodienone than ER alpha-positive MCF-7 and T47D cells. Furanodienone could effectively block 17 beta-estradiol (E2)-stimulated MCF-7 cell proliferation and cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1 DNA content and the appearance of apoptotic nuclei after DAPI staining. Furanodienone specifically down-regulated ER alpha protein and mRNA expression levels without altering ER beta expression. Furanodienone treatment inhibited E2-stimulation of estrogen response element (ERE)-driven reporter plasmid activity and ablated E2-targeted gene (e. g., c-Myc, Bcl-2, and cyclin D1) expression which resulted in the inhibition of cell cycle progression and cell proliferation, and in the induction of apoptosis. Knockdown of ER alpha in MCF-7 cells by ER alpha-specific siRNA decreased the cell growth inhibitory effect of furanodienone. These findings suggest that effects of furanodienone on MCF-7 cells are mediated, at least in part, by inhibiting ER alpha signaling. J. Cell. Biochem. 112: 217-224, 2011. (C) 2010 Wiley-Liss, Inc.