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

Abstract

High-fiber diets have been shown to have beneficial effects on preventing tumorigenesis. Inositol hexaphosphate (InsP 6 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 InsP 6 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 InsP 6 in keratinocytes ( P<0.01). Furthermore, when mouse skin was treated with 10 mM InsP 6, ODC induction was significantly inhibited ( P<0.05). In addition, the expression of TPA-induced c-myc mRNA was significantly inhibited by the same InsP 6 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 InsP 6 treatment were found in HEL-30 cells. These results indicate that InsP 6 reduces TPA-induced ODC activity independent of PKC isoform expression.