Dihydromyricetin induces apoptosis and cytoprotective autophagy through ROS-NF-κB signalling in human melanoma cells

Free Radic Res. 2017 May;51(5):517-528. doi: 10.1080/10715762.2017.1328552.

Abstract

Dihydromyricetin (DHM), a Rattan tea extract, has recently been shown to have anti-cancer activity in mammalian cells. In this study, we investigated the effect of DHM on human melanoma cells. Apart from induction of apoptosis, we demonstrated that DHM induced an autophagic response. Moreover, pharmacological inhibition or genetic blockade of autophagy enhanced DHM-induced cell death and apoptosis, indicating the cytoprotective role of autophagy in DHM-treated human melanoma cells. Further study suggested that the nuclear factor kappa B (NF-κB) signalling pathway was involved in DHM-induced autophagy. Moreover, N-acetyl-cysteine (NAC), an ROS scavenger, abrogated the effects of DHM on NF-κB-dependent autophagy. Taken together, this evidence demonstrates that a strategy of blocking ROS-NF-κB-dependent autophagy to enhance the activity of DHM warrants further attention for the treatment of human melanoma.

Keywords: Dihydromyricetin; NF-κB; apoptosis; autophagy; melanoma; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy
  • Cell Line, Tumor
  • Cytoprotection
  • Drug Screening Assays, Antitumor
  • Flavonols / pharmacology*
  • Humans
  • Melanoma / drug therapy*
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Skin Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Flavonols
  • NF-kappa B
  • Reactive Oxygen Species
  • dihydromyricetin