SAT-461 Regulation of Estrogen Receptor (ERα) and Tumor Suppressor Gene (p53) by Curcumin in MCF-7 Breast Cancer Cells

Abstract S. Pfiffner: None. A. Zanib: None. E. Hallman: None. K. Farrar: None. R. Yaldo: None. N. Prudhomme: None. J. Koujane: None. S. Dinda: None. Curcumin is a golden-yellow flavonoid compound derived from the turmeric (Curcuma longa) plant root that has been used in Chinese and Indian medicine for centuries. Its appeal lies in demonstrated antioxidant, anti-inflammatory, and anti-cancer properties. Studies reveal curcumin exhibits anticancer effects on cancer stem-like cells (CSCs) through the restoration of E-cadherin, a tumor suppressor. Curcumin also demonstrates a significant reduction in breast cancer proliferation in vitro, through a proposed mechanism of p53-induced apoptosis. Given the prevalence and mortality of breast cancer and the protective properties of curcumin, it is imperative to investigate their relationship. Our laboratory previously studied the effects of curcumin on the T-47D breast cancer cell line, which demonstrated significant downregulation of both p53 and ERɑ protein levels with a concomitant decrease in cell viability. Our current study examines the effects of curcumin on ERα, p53, and p21 expression in the MCF-7 breast cancer cell line. We utilized western blot analyses, cellular viability assays, and confocal microscopy during our investigations. In order to deplete any endogenous steroids or effectors, breast cancer cells were cultured in a medium containing 5% charcoal-stripped fetal bovine serum for six days before treatment. Western blotting reveals significant downregulation of ERα in a concentration-dependent manner following treatment with increasing curcumin concentration (5µM-100µM). In the hormone studies, when the treatment of curcumin (40µM) is combined with estradiol, the expression of ERα significantly downregulates, even more so than when treated alone. The effects of curcumin on p53 are also promising, with western blotting revealing a significant concentration-dependent increase in p53 levels with increasing curcumin concentrations (5µM-100µM). Lastly, the effects of curcumin on p21 show a significant concentration-dependent increase in p21 levels with increasing curcumin concentrations (5µM-100µM). Cellular viability studies demonstrate a significant decrease in cellular proliferation after treatment with curcumin, similar to the levels seen with antiestrogens ICI and tamoxifen. RT-qPCR studies in cells revealed a transcriptional expression of ESR1 mRNA levels that correlate with the translational data from western blot analyses. Overall, the effects of curcumin on the MCF-7 breast cancer cell line show significant downregulation of ERα, significant upregulation of p53 and p21, and a significant decrease in breast cancer proliferation. This constellation of findings is promising, and our studies provide a groundwork for further investigation of this compound as it relates to breast cancer progression clinically. Saturday, June 1, 2024