Estrogen receptor-α36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells

J Pharmacol Sci. 2016 Feb;130(2):85-93. doi: 10.1016/j.jphs.2015.12.003. Epub 2015 Dec 15.

Abstract

Epigallocatechin-3-gallate (EGCG) is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER)-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-α, ER-α36. The aim of our present study is to determine the role of ER-α36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-α36 in these cells. However, in ER-α36 knocked-down MDA-MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER-α36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-α36 and EGFR. Thus, our study indicated ER-α36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-α36 positive breast cancer.

Keywords: Cancer stem/progenitor cells; ER-α36; Epigallocatechin-3-gallate; Epithelial growth factor receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Transformation, Neoplastic / drug effects*
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / physiology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Neoplastic Stem Cells / pathology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Estrogen Receptor alpha
  • Catechin
  • epigallocatechin gallate