GROWTH-INHIBITION AND DIFFERENTIATION OF HT-29 CELLS IN-VITRO BY INOSITOL HEXAPHOSPHATE (PHYTIC ACID)

Inositol hexaphosphate (InsP6 or phytic acid) has been shown to have a ntineoplastic action in in vivo models of colon carcinogenesis. We the refore investigated its effect on proliferation and differentiation of the human colon cancer cell line HT-29 in vitro. Proliferation was ev aluated by neutral red incorporation assay, and differentiation was as sessed by expression of the markers, cytokeratin, carcinoembryonic ant igen (CEA) and beta-D-galactose-[1->3]-N-acetyl-galactosamine (Gal-Gal NAc). InsP6 in the culture media (0.66 - 10 mM) inhibited cell prolife ration in a dose-dependent manner (P < 0.001), while inositol or inosi tol hexasulfate used as controls or media without InsP6 did not show a ny suppressive effect. The expression of the tumor marker, Gal-GalNac, was augmented (100.7% increase) by low dose (0.66 mM) of InsP6 but wa s subsequently suppressed with higher concentrations of InsP6. The exp ression of cytokeratin and CEA were both augmented by either InsP6 or inositol at all concentrations tested, although the degree of augmenta tion was milder with inositol than with InsP6. The combination of InsP 6 and inositol (both 0.66 mm) resulted in augmentation (P < 0.001) of cytokeratin expression, while that of CEA remained unchanged. The inhi bitory effect of InSP6 on cell proliferation was not altered by combin ation with additional inositol at any concentrations tested. Our resul ts show that InsP6 inhibits cell proliferation and concomitantly incre ases differentiation and is therefore a candidate chemopreventive and chemotherapeutic agent for human large intestinal cancer.