Inositol hexaphosphate reduces 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase independent of protein kinase C isoform expression in keratinocytes

High-fiber diets have been shown to have beneficial effects on preventing tumorigenesis. Inositol hexaphosphate (InsP₆ or phytic acid) which is a fiber-associated component of cereals and legumes has been demonstrated to inhibit cell proliferation and enhance cell differentiation, indicating its potential for chemopreventive roles. In this study, we investigated the effect of InsP₆ on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity, an essential event in tumor promotion in HEL-30 cells, a murine keratinocyte cell line and SENCAR mouse skin. ODC activity was significantly reduced by 0.5 mM InsP₆ in keratinocytes (P<0.01). Furthermore, when mouse skin was treated with 10 mM InsP₆, ODC induction was significantly inhibited (P<0.05). In addition, the expression of TPA-induced c-myc mRNA was significantly inhibited by the same InsP₆ treatments in HEL-30 cells and CD-1 mouse skin (P<0.01). No changes in protein kinase C (PKC) isoform expression and phorbol dibutyrate binding due to InsP₆ treatment were found in HEL-30 cells. These results indicate that InsP₆ reduces TPA-induced ODC activity independent of PKC isoform expression.