icaritin and Triple-Negative-Breast-Neoplasms

A sub-class of ER-negative breast cancer that is negative for ER, PR and HER2 expression known as triple-negative breast cancer (TNBC) is highly malignant and lacks effective treatment. Recently, it has been reported that an isoform of estrogen receptor-alpha ER-α36 is expressed and plays a critical role in development of TNBC. ER-α36 forms a positive regulatory loop with epidermal growth factor receptor (EGFR), which promotes malignant growth of TNBC cells. Thus, ER-α36 has been proposed as an important target for development of novel drugs for TNBC. In this study, we evaluated the effects of icaritin, a prenylflavonoid derivant purified from Epimedium Genus, on growth of TNBC cells and examined the possible underlying mechanisms. Our study demonstrated that icartin decreased both ER-α36 and EGFR protein expression, and induced apoptosis in TNBC MDA-MB-231 and MDA-MB-453 cells. We also found that icaritin inhibited ER-α36-mediated MAPK/ERK pathway and cyclin D1 induction by estrogen. Our results thus indicated that icaritin has a potential to be developed into a novel therapeutic agent for human TNBC.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Epimedium; ErbB Receptors; Estrogen Antagonists; Estrogen Receptor alpha; Estrogens; Female; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Neoplasm Proteins; Promoter Regions, Genetic; Recombinant Proteins; RNA Interference; Triple Negative Breast Neoplasms