Inositol hexaphosphate inhibits ultraviolet B-induced signal transduction

Inositol hexaphosphate (InsP(6)) 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 associa ted with UVB-induced carcinogenesis. Here we report the effects of InSP6 on UVB-induced signal transduction. InsP(6) strongly blocked UVB-induced acti vator protein-1 (AP-1) and NF-kappaB transcriptional activities in a dose-d ependent manner. InsP(6) also suppressed UVB-induced AP-1 and nuclear facto r kappaB (NF-kappaB) DNA binding activities and inhibited UVB-induced phosp horylation of extracellular signal-regulated protein kinases (Erks) and c-J un NH2-terminal kinases (JNKs). Phosphorylation of p38 kinases was not affe cted. InsP(6) also blocked UVB-induced phosphorylation of I kappaB-alpha, w hich is known to result in the inhibition of NF-kappaB transcriptional acti vity. InSP6 does not block UVB-induced phosphotidylinositol-3' (PI-3) kinas e activity, suggesting that the inhibition of UVB-induced AP-1 and NF-kappa B 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 carcinog enesis by inhibiting AP-1 and NF-kappaB transcription activities. (C) 2001 Wiley-Liss, Inc.