Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway

Food Chem Toxicol. 2013 Jan:51:53-60. doi: 10.1016/j.fct.2012.09.012. Epub 2012 Sep 18.

Abstract

Previous studies have demonstrated that wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities. In this study, we evaluated wogonoside-induced autophagy on human breast MDA-MB-231 cells. We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells. In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris. The results showed that wogonoside promotes the expression of LC3-II and Beclin-1. Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which was associated with wogonoside-induced autophagy. Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Flavanones / pharmacology*
  • Glucosides / pharmacology*
  • Humans
  • Lysosomes / drug effects
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation / drug effects
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Vacuoles / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Flavanones
  • Glucosides
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • wogonoside