Er Alpha Is A Target For Butein-Induced Growth Suppression In Breast Cancer

Breast cancer (BCa) has the highest incidence and mortality among malignant diseases in female worldwide. BCa is frequently caused by estrogen receptor alpha (ER alpha), a ligand-dependent receptor that highly expressed about 70% of breast tumors. Therefore, ER alpha has become a well-characterized and the most effective target for treating ER alpha-expressing BCa (ER alpha(+) BCa). However, the acquire resistance was somehow developed in patients who received current ER alpha signaling-targeted endocrine therapies. Hence, discovery of novel anti-estrogen/ER alpha strategies is urgent. In the present study, we identified butein as a potential agent for breast cancer treatment by the use a natural product library. We showed that butein inhibits the growth of ER alpha(+) BCa both in vitro and in vivo which is associated with cell cycle arrest that partially triggered by butein-induced ER alpha downregulation. Mechanically, butein binds to a specific pocket of ER alpha and promotes proteasome-mediated degradation of the receptor. Collectively, this work reveals that butein is a candidate to diminish ER alpha signaling which represents a potentially novel strategy for treating BCa.