Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment

The incidence and mortality of breast cancer (BCa) are the highest among female cancers. There are approximate 70% BCa that are classified as estrogen receptor alpha (ER) positive. Therefore, targeting ER is the most significantly therapeutic schedule. However, patients with breast cancer develop resistance to ER or estrogen (E2) antagonists such as fulvestrant and tamoxifen. In the present study, we found that L-Tetrahydropalmatine (L-THP) significantly suppressed cell proliferation in ER + BCa cells via inducing cell cycle arrest rather than apoptosis. Additionally, L-THP enhanced the sensitivity of ER + BCa cells to tamoxifen and fulvestrant. Mechanically, the application of L-THP promotes ER degradation through accumulating ubiquitin chains on ER. Overexpressing ER abrogates L-THP induced-antiproliferation in ER + BCa cells. Collectively, our work indicates that L-THP may represent a potentially novel therapeutic medicine for ER + breast cancer patient.