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[³H]Inositol Hexaphosphate (Phytic Acid) is Rapidly Absorbed and Metabolized by Murine and Human Malignant Cells in Vitro^{1, 2, 3,}

Department of Medical and Research Technology ^* Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201

To test the hypothesis that the antineoplastic activity of phytic acid [inositol hexaphosphate (InsP₆)] is a result of rapid intake by the cells and its conversion to lower inositol phosphates (InsP_1–5), thereby affecting the intracellular inositol phosphate pool, YAC-1 (mouse T cell leukemia), K562 (human erythroleukemia) and HT-29 (human colon adenocarcinoma) cell lines were incubated at 37°C with [³H]InsP₆. After 1 h, 31.3 ± 3.1% of administered radioactivity was taken up by YAC-1 cells, 6.2 ± 0.9% by K562 cells and 6.6 ± 3.8% by HT-29 cells. Differential centrifugation and high resolution subcellular fractionation of cell homogenates demonstrated that within the various cellular compartments, 80% (HT-29) to 97% (YAC-1) of the total radioactivity was in the cytosol. Kinetic study showed that the peak of the total absorption was obtained after 30 min of cell exposure to radiolabeled InsP₆, after with a plateau was reached. Analysis of the radioactivity accumulated within the cells showed variable proportions of myo-inositol and InsP_1–6, with a preponderance of InsP₁ and InsP₂. The presence of [³H]myo-inositol and [³H]InsP_1–6 suggests that InsP₆ may, in some cells at least, be absorbed as such and that a variable degree of dephosphorylation of InsP₆ takes place both extra- and intracellularly.

KEY WORDS: • inositol hexaphosphate • second messenger • phytic acid • antineoplastic • signal transduction

¹ Presented at the Annual Meeting of the Federation of American Societies for Experimental Biology, April 5–9, 1992, Anaheim, CA (Vucenik, I., Sakamoto, K. & Shamsuddin, A. M. (1992) In vitro uptake of inositol hexaphosphate (InsP₆) by malignant cells. FASEB J. 6: A1392 (abs.)].

² Supported in part by American Institute for Cancer Research grant 91SG04 and by Special Research Initiative Support Awards from the University of Maryland at Baltimore Designated Research Initiative Fund (I. V. and A.M.S.).

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 28 June 1993. Revision accepted 14 January 1994.