Phloretin Inhibits the Proliferation of Breast Cancer Cells Through the Down-regulation of Estrogen Receptor α

Background/Aim: Phloretin is a natural flavonoid compound found in some plants, such as apples and pears, as well as in the bark of apple trees. Phloretin has been shown to have inhibitory effects on glucose transporters in cells and can potentially inhibit the growth of cancer cells. However, the mechanism by which phloretin regulates the expression of estrogen receptor alpha (ER alpha), a key transcription factor in breast cancer, is still unclear. This study investigated how phloretin affects the growth of ER alpha positive human breast cancer cells. Materials and Methods: The growth of breast cancer cell lines, including MCF7 and T47D, was examined using cell proliferation and colony formation assays. Western blotting and semi -quantitative RTPCR were used to examine protein and mRNA levels, respectively. Localization of cellular proteins was analyzed using subcellular fractionation. Transient transfection and reported gene assays were used to elucidate the impact of phloretin on cell proliferation and ER alpha transactivation. Results: Phloretin decreased ER alpha expression at the mRNA and protein levels in MCF7 and T47D cells. It also inhibited the binding of ER alpha to the estrogen response element present in the promoter of target genes. Moreover, treatment with phloretin inhibited the expression of cyclin D1 and breast cancer marker gene pS2, which are known ER alpha target genes. Consequently, it inhibited the growth of ER alpha-positive human breast cancer cells. Furthermore, inhibition of breast cancer growth by phloretin was found to be mediated through both the ER alpha and ERK1/ERK2 pathways. Conclusion: Phloretin, a dihydrochalcone extracted from natural sources, exhibits the ability to regulate ER alpha function and suppress breast cancer cell proliferation.