Zinc Induces Apoptosis of Human Melanoma Cells, Increasing Reactive Oxygen Species, p53 and FAS Ligand

Anticancer Res. 2015 Oct;35(10):5309-16.


The aim of this study was to examine the in vitro effect of zinc on the apoptosis of human melanoma cells, by studying the zinc-dependent modulation of intracellular levels of reactive oxygen species (ROS) and of p53 and FAS ligand proteins. We showed that zinc concentrations ranging from 33.7 μM to 75 μM Zn(2+) induced apoptosis in the human melanoma cell line WM 266-4. This apoptosis was associated with an increased production of intracellular ROS, and of p53 and FAS ligand protein. Treatment of tumor cells with the antioxidant N-acetylcysteine was able to prevent Zn(2+)-induced apoptosis, as well as the increase of p53 and FAS ligand protein induced by zinc. Zinc induces apoptosis in melanoma cells by increasing ROS and this effect may be mediated by the ROS-dependent induction of p53 and FAS/FAS ligand.

Keywords: FAS ligand; Melanoma; apoptosis; p53; reactive oxygen species; zinc.

MeSH terms

  • Acetylcysteine / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fas Ligand Protein / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / drug therapy
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Reactive Oxygen Species / metabolism
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Suppressor Protein p53 / metabolism
  • Zinc / pharmacology*


  • Antineoplastic Agents
  • FASLG protein, human
  • Fas Ligand Protein
  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Zinc
  • Acetylcysteine