AnvirzelTMregulates cell death through inhibiting GSK-3 activity in human U87 glioma cells

Neurol Res. 2020 Jan;42(1):68-75. doi: 10.1080/01616412.2019.1709744. Epub 2020 Jan 3.

Abstract

Objectives: Cardiac glycosides are used as potential anti-cancer agents due to their effects on the inhibition of proliferation and induction of apoptosis and/or autophagy in cancer cells. Herein, we aimed to study the potential signaling pathways taken role in differential cell-death properties of AnvirzelTM which is consisted of two toxic cardiac glycosides (oleandrin and oleandrigenin), in U87 human glioblastoma cells.Methods: The anti-proliferative and anti-migratory effects of AnvirzelTM were assessed in U87 cells by WST-1 assay and wound healing assay, respectively. After treatment of AnvirzelTMwith doses of 10, 25, 50, 100 and 250 μg/ml, expression levels of proteins related to cell death were investigated by Western blot.Results: Anvirzel™ markedly inhibited the growth of U87 cells in a time- and dose-dependent manner following 24 h and 48 h treatments (p < 0.05). In addition, it was found that Anvirzel™ inhibited GSK-3, NOS and HIF1-α expressions whereas activated ERK in U87 cells compared to vehicle (p < 0.05).Discussion: The results suggested that AnvirzelTM regulated cell death distinctly from apoptosis in human glioblastoma cells. Further studies are required for validation of mechanistic insights about the potential signaling pathways taken role in differential cell death properties of AnvirzelTM.

Keywords: Anvirzel™; GSK-3 kinase; cell death; glioblastoma; oleandrin.

MeSH terms

  • Cardenolides / pharmacology*
  • Cardiac Glycosides / pharmacology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Humans

Substances

  • Anvirzel
  • Cardenolides
  • Cardiac Glycosides
  • Enzyme Inhibitors
  • Glycogen Synthase Kinase 3