Int J Biol Sci 2020; 16(12):2192-2204. doi:10.7150/ijbs.44005

Research Paper

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

Xiaohong Xia1,2,*, Jinchan He2,*, Bin Liu1,*, Zhenlong Shao2, Qiong Xu1, Tumei Hu2, Cuifu Yu2, Xiaolin Liu1, Yuning Liao2, Ningning Liu1,✉, Hongbiao Huang2,✉

1. Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510260, China
2. Affiliated Cancer Hospital & institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou, Guangdong 511436, China
*These authors contributed equally to this work.

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Citation:
Xia X, He J, Liu B, Shao Z, Xu Q, Hu T, Yu C, Liu X, Liao Y, Liu N, Huang H. Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment. Int J Biol Sci 2020; 16(12):2192-2204. doi:10.7150/ijbs.44005. Available from http://www.ijbs.com/v16p2192.htm

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Abstract

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

Keywords: breast cancer, L-THP, ERα, proliferation, cell cycle