Resveratrol triggers protective autophagy through the ceramide/Akt/mTOR pathway in melanoma B16 cells

Nutr Cancer. 2014;66(3):435-40. doi: 10.1080/01635581.2013.878738. Epub 2014 Feb 28.

Abstract

Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RSV), a natural polyphenolic compound, is known as a promising anti-cancer agent. In this study, we showed that RSV could inhibit the growth of B16 cells via induction of apoptosis. Moreover, our results showed for the first time that RSV induced autophagy in B16 cells, which might occur through ceramide accumulation and Akt/mTOR pathway inhibition. Inhibition of autophagy by an autophagic inhibitor 3-methyladenine (3-MA) or si-Beclin 1 enhanced RSV-induced cytotoxicity and apoptosis. Thus, autophagy inhibition represents a promising approach to improve the efficacy of RSV in the treatment of patients with melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Autophagy
  • Beclin-1
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Ceramides / metabolism*
  • Gene Knockdown Techniques
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, mouse
  • Ceramides
  • RNA, Small Interfering
  • Stilbenes
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Resveratrol