Snake venom toxin inhibits cell growth through induction of apoptosis in neuroblastoma cells

Arch Pharm Res. 2009 Nov;32(11):1545-54. doi: 10.1007/s12272-009-2106-0.

Abstract

Snake venom toxin from Vipera lebetina turanica can induce apoptosis in many cancer cell lines, but there is no study about the apoptotic effect of snake venom toxin on human neuroblastoma cells. In this study, we investigated the apoptotic effect of snake venom toxin in human neuroblastoma SK-N-MC and SK-N-SH cells. Our result showed that cell detachment and apoptotic cell death were increased by snake venom toxin (1.25-10 microg/mL), but normal neuronal cells were not affected. Consistent with the induction of apoptosis, the level of reactive oxygen species (ROS) was increased, but mitochondrial membrane potential (MMP) was disrupted by treatment with snake venom toxin. However, the glutathione prevented snake venom toxin-induced cell growth inhibition. Snake venom toxin also increased the expression of pro-apoptotic protein Bax, but down-regulated anti-apoptotic protein Bcl-2. Therefore, these results showed that snake venom toxin from Vipera lebetina turanica causes apoptotic cell death of neuroblastoma cells through ROS dependent MMP disruption, and suggested that snake venom toxin may be applicable as an anti-cancer agent for neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroblastoma / drug therapy*
  • Neurons / drug effects
  • Neurons / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Reactive Oxygen Species / metabolism
  • Viper Venoms / administration & dosage
  • Viper Venoms / pharmacology*
  • Viperidae*
  • bcl-2-Associated X Protein / drug effects
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Viper Venoms
  • bcl-2-Associated X Protein