Huaier polysaccharide inhibits the stem-like characteristics of ERα-36high triple negative breast cancer cells via inactivation of the ERα-36 signaling pathway

Int J Biol Sci. 2019 May 20;15(7):1358-1367. doi: 10.7150/ijbs.27360. eCollection 2019.

Abstract

Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies. It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC. Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients. Huaier polysaccharide (HP), an active ingredient extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anti-cancer treatments in China. Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cells in vitro, and inhibited xenograft tumor formation in vivo. Mechanically, HP markedly reduced the expression of estrogen receptor α-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/β-catenin signaling in ERα-36high TNBC cells. This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.

Keywords: Cancer stem cells; ERα-36; Huaier; Triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales
  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Complex Mixtures / pharmacology*
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / metabolism*
  • Polysaccharides / pharmacology
  • Signal Transduction*
  • Trametes
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / therapy*
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Complex Mixtures
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Polysaccharides
  • beta Catenin
  • huaier