Phytate hydrolysate induces circumferential F-actin ring formation at cell-cell contacts by a Rho-associated kinase-dependent mechanism in colorectal cancer HT-29 cells.
Phytate (inositol hexa-phosphate or IP6) possessing anticancer activity is hydrolyzed by phytase in intestinal microbes and the metabolites are distributed throughout the colon. Cellular circumferential F-actin rings, which are involved in cell polarity and structure, are lost early during tumorigenesis. We investigated F-actin ring formation by the phytate hydrolysate in colorectal cancer HT-29 cells to explore the novel mechanisms underlying the phytate-mediated anticancer function. The phytate hydrolysate, but not inositol or phytate, induced F-actin ring formation with a peak at 10 min in the cells and was associated with phosphorylation of myosin regulatory light chain. F-actin ring formation and myosin regulatory light chain phosphorylation by the phytate hydrolysate were suppressed by inhibitors of Rho-associated kinase (ROCK), Janus kinase (JAK), c-Jun N-terminal kinase (JNK), and protein kinase Cδ (PKCδ). Activation of ROCK and JAK, but not JNK or PKCδ, was observed at 10 min and/or earlier after stimulation with the phytate hydrolysate. Altogether, the phytate hydrolysate induces circumferential F-actin ring formation through a ROCK-dependent myosin II activation in the HT-29 cells, which requires JAK activation and basal activities of JNK and PKC. Hydrolysis products of phytate in the intestine may contribute to anticancer function of phytate.
Suzuki
Takuya
T
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Japan.
Hara
Hiroshi
H
D000199:Actins / Q000378:metabolism*; D000704:Analysis of Variance; D019073:HT29 Cells; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016014:Linear Models; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D010833:Phytic Acid / Q000494:pharmacology*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism*
D000199:Actins; D007295:Inositol Phosphates; D018994:Myosin Light Chains; D010833:Phytic Acid; D054460:rho-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases