Cyanidin-3-o-glucoside directly binds to ERα36 and inhibits EGFR-positive triple-negative breast cancer

Abstract

// Li Wang 1, * , Haifeng Li 1, * , Shiping Yang 1 , Wenqiang Ma 1 , Mei Liu 2 , Shichao Guo 1 , Jun Zhan 3 , Hongquan Zhang 3 , Suk Ying Tsang 4 , Ziding Zhang 1 , Zhaoyi Wang 5 , Xiru Li 2 , Yang-Dong Guo 1 , Xiangdong Li 1 1 State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China 2 Department of General Surgery, The 301th Hospital of PLA, Beijing, China 3 Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, China 4 School of Life Sciences and State Key Laboratory of Agro-Biotechnology, Chinese University of Hong Kong, Hong Kong, China 5 Beijing Shenogen Pharma Group, Beijing, China * These authors have contributed equally to this work Correspondence to: Yang-Dong Guo, email: [e-mail] Xiru Li, email: [e-mail] Zhaoyi Wang, email: [e-mail] Xiangdong Li, email: [e-mail] Keywords: Cy-3-glu, ERα36, EGFR, triple-negative breast cancer, apoptosis Received: December 03, 2015     Accepted: September 02, 2016     Published: September 15, 2016 ABSTRACT Anthocyanins have been shown to inhibit the growth and metastatic potential of breast cancer (BC) cells. However, the effects of individual anthocyanins on triple-negative breast cancer (TNBC) have not yet been studied. In this study, we found that cyanidin-3-o-glucoside (Cy-3-glu) preferentially promotes the apoptosis of TNBC cells, which co-express the estrogen receptor alpha 36 (ERα36) and the epidermal growth factor receptor (EGFR). We demonstrated that Cy-3-glu directly binds to the ligand-binding domain (LBD) of ERα36, inhibits EGFR/AKT signaling, and promotes EGFR degradation. We also confirmed the therapeutic efficacy of Cy-3-glu on TNBC in the xenograft mouse model. Our data indicates that Cy-3-glu could be a novel preventive/therapeutic agent against the TNBC co-expressed ERα36/EGFR.