Abstract
Abstract The estrogen receptor alpha (ERα), a nuclear receptor and transcription factor governs the action of estrogen. This hormone is the major contributor to normal breast development and breast carcinogenesis. Thus, antiestrogens are widely utilized to treat and circumvent the progression of hormone receptor positive breast cancer. However, resistance to these agents develops after sustained use and major risk factors such as enhanced susceptibility to endometrial cancer have been associated with this type of treatment. In an effort to develop natural therapeutic compounds against ERα positive breast cancer, the effect of deguelin, a rotenoid isolated from an African plant; Mundulea sericea on ERα positive human breast cancer cells was investigated. Here we report that deguelin treatment downregulated the expression of ERα protein in a dose dependent manner in MCF-7 and T47D human breast cancer cell lines as determined by immunoblotting. Quantitative RT-PCR analysis revealed that the mRNA expression of ERα target genes Cathepsin D (CTSD), Trefoil factor 1 (TFF1) and the Progesterone receptor (PGR) was also downregulated by 50% in the presence of deguelin in MCF-7 cells. Furthermore, deguelin treatment significantly inhibited the proliferation of these two cell lines. Importantly, estrogen mediated stimulation of cell growth was reduced by 30% in MCF-7 cells after deguelin treatment. Together these findings suggest that deguelin suppresses ERα signaling, paving the way for the development of a novel natural therapeutic agent against endocrine receptor positive breast cancer. Future studies are aimed at deciphering the molecular mechanisms by which deguelin adversely affects ERα function. (This work was supported by NCI CA140321). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 573. doi:1538-7445.AM2012-573
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