Inositol hexaphosphate inhibits ultraviolet B-induced signal transduction.
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.
Chen
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Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Ma
W Y
WY
Dong
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000528:radiation effects; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010833:Phytic Acid / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D010833:Phytic Acid; D004247:DNA; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D000077191:Wortmannin