The anti-tumor efficiency of pterostilbene is promoted with a combined treatment of Fas signaling or autophagy inhibitors in triple negative breast cancer cells

Food Funct. 2014 Aug;5(8):1856-65. doi: 10.1039/c4fo00145a.

Abstract

High expression of vimentin, a canonical mesenchymal marker, is linked with poor prognosis in triple negative breast cancer (TNBC), implying that vimentin may be a potential biomarker in the application of TNBC therapy. Pterostilbene (PTE) has shown anti-invasion activity, and thus, we investigated whether PTE inhibited the epithelial-mesenchymal transition (EMT) in TNBC. Here, we show that PTE decreases the vimentin expression, but that the effect was transient. PTE stimulated Fas signaling, which drives EMT by the ERK1/2 and GSK3β/β-catenin pathways, supporting Fas signaling induction involved in EMT regulation. PTE also triggered autophagy in TNBC. The treatment of TNBC with 3-methyladenine an autophagy inhibitor, not only sustained PTE-inhibited EMT but also significantly promoted anti-proliferation, which indicates that autophagy plays a cyto-protective role and is associated with EMT. Taken together, these data showed that Fas signaling and autophagy accelerated the aggressiveness of TNBC. Inhibition of autophagy or Fas signaling may provide novel targets for TNBC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagy / drug effects*
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • Triple Negative Breast Neoplasms / metabolism*
  • Vimentin / antagonists & inhibitors
  • Vimentin / genetics
  • Vimentin / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism
  • fas Receptor / genetics
  • fas Receptor / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • FAS protein, human
  • Stilbenes
  • Vimentin
  • beta Catenin
  • fas Receptor
  • pterostilbene
  • 3-methyladenine
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Adenine