title: Cyanidin-3-o-glucoside directly binds to ERα36 and inhibits EGFR-positive triple-negative breast cancer.
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.
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of General Surgery, The 301th Hospital of PLA, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhan
authors.affiliation: 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.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Life Sciences and State Key Laboratory of Agro-Biotechnology, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Suk Ying
authors.initials: SY
authors.lastname: Tsang
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Shenogen Pharma Group, Beijing, China.
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The 301th Hospital of PLA, Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Yang-Dong
authors.initials: YD
authors.lastname: Guo
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D008928:Mitochondria / Q000378:metabolism; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000872:Anthocyanins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005960:Glucosides; C462279:cyanidin-3-O-beta-glucopyranoside; D013482:Superoxide Dismutase; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Cy-3-glu; EGFR; ERα36; apoptosis; triple-negative breast cancer