[3H]inositol hexaphosphate (phytic acid) is rapidly absorbed and metabolized by murine and human malignant cells in vitro.
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 (InsP1-5), 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 degrees C with [3H]InsP6. After 1 h, 31.3 +/- 3.1% of administered radio-activity 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 InsP1-6, with a preponderance of InsP1 and InsP2. The presence of [3H]myo-inositol and [3H]InsP1-6 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.
Vucenik
I
I
Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201.
Shamsuddin
A M
AM
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002852:Chromatography, Ion Exchange; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism*; D051379:Mice; D010833:Phytic Acid / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D010833:Phytic Acid