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

Oncotarget. 2016 Oct 18;7(42):68864-68882. doi: 10.18632/oncotarget.12025.

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

  • Animals
  • Anthocyanins / chemistry
  • Anthocyanins / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucosides / pharmacology*
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Microcirculation
  • Mitochondria / metabolism
  • Neoplasm Transplantation
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Superoxide Dismutase / metabolism
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism

Substances

  • Anthocyanins
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Glucosides
  • cyanidin-3-O-beta-glucopyranoside
  • Superoxide Dismutase
  • EGFR protein, human
  • ErbB Receptors
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt