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.
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907-1264, USA. kwang@cfs.purdue.edu
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D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D015603:Keratinocytes / Q000201:enzymology*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D065108:Ornithine Decarboxylase Inhibitors; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010833:Phytic Acid / Q000494:pharmacology*; D011493:Protein Kinase C / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007527:Isoenzymes; D065108:Ornithine Decarboxylase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D010833:Phytic Acid; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate