Inositol hexaphosphate inhibits ultraviolet B-induced signal transduction

Mol Carcinog. 2001 Jul;31(3):139-44. doi: 10.1002/mc.1048.

Abstract

Inositol hexaphosphate (InsP6) has an effective anticancer action in many experimental models in vivo and in vitro. Ultraviolet B (UVB) radiation is believed to be responsible for many of the carcinogenic effects related to sun exposure, and alteration in UVB-induced signal transduction is associated with UVB-induced carcinogenesis. Here we report the effects of InsP6 on UVB-induced signal transduction. InsP6 strongly blocked UVB-induced activator protein-1 (AP-1) and NF-kappaB transcriptional activities in a dose-dependent manner. InsP6 also suppressed UVB-induced AP-1 and nuclear factor kappaB (NF-kappaB) DNA binding activities and inhibited UVB-induced phosphorylation of extracellular signal-regulated protein kinases (Erks) and c-Jun NH2-terminal kinases (JNKs). Phosphorylation of p38 kinases was not affected. InsP6 also blocked UVB-induced phosphorylation of IkappaB-alpha, which is known to result in the inhibition of NF-kappaB transcriptional activity. InsP6 does not block UVB-induced phosphotidylinositol-3' (PI-3) kinase activity, suggesting that the inhibition of UVB-induced AP-1 and NF-kappaB activities by InsP6 is not mediated through PI-3 kinase. Because AP-1 and NF-kappaB are important nuclear transcription factors that are related to tumor promotion, our work suggests that InsP6 prevents UVB-induced carcinogenesis by inhibiting AP-1 and NF-kappaB transcription activities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Blotting, Western
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / radiation effects
  • Luciferases / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Phytic Acid / pharmacology*
  • Protein Binding / drug effects
  • Signal Transduction / drug effects*
  • Signal Transduction / radiation effects*
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic
  • Ultraviolet Rays*
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • NF-kappa B
  • Transcription Factor AP-1
  • Phytic Acid
  • DNA
  • Luciferases
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • Wortmannin