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.
Keywords:
Cy-3-glu; EGFR; ERα36; apoptosis; triple-negative breast cancer.
MeSH terms
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Animals
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Anthocyanins / chemistry
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Anthocyanins / pharmacology*
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Apoptosis
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Cell Cycle
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Cell Line, Tumor
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Cell Proliferation
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Cell Survival
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Estrogen Receptor alpha / metabolism*
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Female
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Gene Expression Regulation, Neoplastic
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Glucosides / pharmacology*
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Humans
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MCF-7 Cells
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Mice
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Mice, Inbred BALB C
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Microcirculation
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Mitochondria / metabolism
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Neoplasm Transplantation
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Oligonucleotide Array Sequence Analysis
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Protein Binding
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Proto-Oncogene Proteins c-akt / metabolism
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Superoxide Dismutase / metabolism
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Triple Negative Breast Neoplasms / drug therapy*
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Triple Negative Breast Neoplasms / metabolism
Substances
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Anthocyanins
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ESR1 protein, human
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Estrogen Receptor alpha
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Glucosides
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cyanidin-3-O-beta-glucopyranoside
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Superoxide Dismutase
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EGFR protein, human
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ErbB Receptors
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt