Celastrol inhibits the growth of estrogen positive human breast cancer cells through modulation of estrogen receptor alpha

Human estrogen receptor a (ER alpha) is a nuclear transcription factor that displays a major therapeutic target for breast cancer The transcriptional activity of ER alpha can be regulated by particular estrogen receptor modulators Celastrol a quinine methide triterpene extracted from a Chinese medicine (Topterygium wilfordii! Hook F) has been reported to have therapeutic efficacy against various cancer cells including prostate cancer leukemia and melanoma cells However ER alpha regulation by Celastrol has not been reported In this study we investigated the effects of Celastrol on the growth of breast cancer cells We observed that Celastrol decreased expression of ER alpha at both the mRNA and the protein levels in MCF7 and T47D human breast cancer cells Results from a luciferase assay showed that Celastrol decreased the transcriptional activity of ER alpha Also Celastrol treatment inhibited ER alpha target gene expression including expressions of cyclin D-1 progesterone receptor (PR) and c-Myb leading to cell cycle arrest and growth inhibition of breast cancer cells We propose that Celastrol an anti-cancer drug extracted from natural sources Induces inhibition of cell growth through modulation of ER alpha in estrogen positive breast cancer cells and is a candidate for use in cancer chemotherapy for human breast cancer (c) 2010 Elsevier Ireland Ltd All rights reserved