title: Dose-dependent inhibition of large intestinal cancer by inositol hexaphosphate in F344 rats.
abstract: We have previously reported that inositol hexaphosphate (InsP6) inhibits mitosis and large intestinal cancer (LIC) in F344 rats and CD1 mice when given as 1 or 2% solution in drinking water at the unadjusted pH of 11.3. The purpose of this study was to determine whether InsP6 (i) shows a dose-response inhibition of LIC, and (ii) retains its anti-neoplastic effect at physiological pH. Since InsP6 is known to be a chelator of divalent cations, in preparation for putative clinical trials in humans, we also looked at the mineral bioavailability. F344 rats were fed 0.1% (pH 10.8), 1% (pH 11.3) and 1% (pH 7.4) Na-InsP6 in drinking water. Two weeks following the beginning of InsP6 supplementation, rats were given six injections of azoxymethane (AOM) at a dose of 8 mg/kg body wt/week and were killed 30 weeks following the last injection. Compared to the untreated control rats injected with AOM, 1% InsP6 (pH 11.3) reduces tumor prevalence by 52.2% (P less than 0.01), tumor frequency by 55.8% (P = 0.001) and tumor size by 62.3% (P = 0.001); 0.1% InsP6 showed a lesser reduction in tumor prevalence (21%) but a greater reduction in tumor size 71% (P = 0.001). While there was no significant difference in tumor prevalence and frequency between the two pH groups, the tumor size following 1% InsP6 (pH 7.4) was the smallest (65% smaller than those of pH 11.3, P less than 0.005). There was no significant difference in the serum Mg2+, Ca2+, Fe2+ and Zn2+ level between control rats and those treated with 1% InsP6. We therefore demonstrate that InsP6 (i) is consistently anti-neoplastic for LIC in a dose-dependent manner, (ii) retains its anti-neoplastic activity at physiological pH and (iii) has no demonstrable toxic effect on long-term administration as evident by body wt data and serum mineral levels.
authors: Department of Pathology, University of Maryland, School of Medicine, Baltimore 21201.
authors: A
authors: A
authors: Ullah
authors: A M
authors: AM
authors: Shamsuddin
mesh_terms: D000818:Animals; D001397:Azoxymethane; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D007420:Intestine, Large / Q000187:drug effects; D007501:Iron / Q000097:blood; D008274:Magnesium / Q000097:blood; D010833:Phytic Acid / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D015032:Zinc / Q000097:blood
chemical_list: D010833:Phytic Acid; D007501:Iron; D008274:Magnesium; D015032:Zinc; D001397:Azoxymethane; D002118:Calcium