Pterostilbene induce autophagy on human oral cancer cells through modulation of Akt and mitogen-activated protein kinase pathway

Oral Oncol. 2015 Jun;51(6):593-601. doi: 10.1016/j.oraloncology.2015.03.007. Epub 2015 Apr 14.

Abstract

Objectives: Extensive research supports the administration of herbal medicines or natural foods during cancer therapy. Pterostilbene, a naturally occurring phytoalexin, has various pharmacological activities, including antioxidant activity, cancer prevention activity, and cytotoxicity to many cancers. However, the effect of pterostilbene on the autophagy of tumor cells has not been clarified.

Materials and methods: In this study, the unique effects of pterostilbene on the autophagy of human oral cancer cells were investigated.

Results: The results of this study showed that pterostilbene effectively inhibited the growth of human oral cancer cells by inducing cell cycle arrest and apoptosis. In addition, the formation of acidic vesicular organelles and LC3-II production also demonstrated that pterostilbene induced autophagy. Administering 3-methylamphetamine (3-MA) and bafilomycin A1 (BafA1) exerted differing effects on the pterostilbene-induced death of human oral cancer cells. Pterostilbene-induced autophagy was triggered by activation of JNK1/2 and inhibition of Akt, ERK1/2, and p38.

Conclusion: In conclusion, this study demonstrated that pterostilbene caused autophagy and apoptosis in human oral cancer cells, suggesting that pterostilbene could serve as a new and promising agent for treating human oral cancer.

Keywords: Apoptosis; Autophagy; MAPK; Oral cancer; Phytoalexin; Pterostilbene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Enzyme Inhibitors / pharmacology
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Macrolides / pharmacology
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Mouth Neoplasms / metabolism*
  • Organelles / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Stilbenes / pharmacology*

Substances

  • 3-methylamphetamine
  • Amphetamines
  • Enzyme Inhibitors
  • MAP1LC3A protein, human
  • Macrolides
  • Microtubule-Associated Proteins
  • Stilbenes
  • pterostilbene
  • bafilomycin A1
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases