AbstractInositol 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‐κB transcriptional activities in a dose‐dependent manner. InsP6 also suppressed UVB‐induced AP‐1 and nuclear factor κB (NF‐κB) 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 IκB‐α, which is known to result in the inhibition of NF‐κB 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‐κB activities by InsP6 is not mediated through PI‐3 kinase. Because AP‐1 and NF‐κB 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‐κB transcription activities. © 2001 Wiley‐Liss, Inc.