Targeting Er Alpha 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 alpha) positive. Therefore, targeting ER alpha is the most significantly therapeutic schedule. However, patients with breast cancer develop resistance to ER alpha 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 alpha(+) BCa cells via inducing cell cycle arrest rather than apoptosis. Additionally, L-THP enhanced the sensitivity of ER alpha(+) BCa cells to tamoxifen and fulvestrant. Mechanically, the application of L-THP promotes ER alpha degradation through accumulating ubiquitin chains on ER alpha. Overexpressing ER alpha abrogates L-THP induced-antiproliferation in ER alpha(+) BCa cells. Collectively, our work indicates that L-THP may represent a potentially novel therapeutic medicine for ER alpha(+) breast cancer patient.