Vucenik I, Shamsuddin A M
Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201.
J Nutr. 1994 Jun;124(6):861-8. doi: 10.1093/jn/124.6.861.
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.
为了验证植酸[肌醇六磷酸（InsP6）]的抗肿瘤活性是细胞快速摄取并转化为较低级肌醇磷酸（InsP1 - 5），从而影响细胞内肌醇磷酸池的结果这一假说，将YAC - 1（小鼠T细胞白血病）、K562（人红白血病）和HT - 29（人结肠腺癌）细胞系于37℃用[3H]InsP6进行孵育。1小时后，YAC - 1细胞摄取了31.3±3.1%的给药放射性活度，K562细胞摄取了6.2±0.9%，HT - 29细胞摄取了6.6±3.8%。对细胞匀浆进行差速离心和高分辨率亚细胞分级分离表明，在各个细胞区室中，总放射性活度的80%（HT - 29）至97%（YAC - 1）存在于胞质溶胶中。动力学研究表明，细胞暴露于放射性标记的InsP6 30分钟后达到总吸收峰值，之后达到平台期。对细胞内积累的放射性活度分析显示，肌醇和InsP1 - 6的比例各不相同，其中InsP1和InsP2占优势。[3H]肌醇和[3H]InsP1 - 6的存在表明，至少在某些细胞中，InsP6可能原样被吸收，并且InsP6在细胞外和细胞内均发生不同程度的去磷酸化。
