A novel mechanism underlying phytate-mediated biological action-phytate hydrolysates induce intracellular calcium signaling by a Gαq protein-coupled receptor and phospholipase C-dependent mechanism in colorectal cancer cells
✍ Scribed by Takuya Suzuki; Teruhiro Nishioka; Satoshi Ishizuka; Hiroshi Hara
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 508 KB
- Volume
- 54
- Category
- Article
- ISSN
- 1613-4125
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✦ Synopsis
Phytate (inositol hexa-phosphate, IP6) possesses multiple biological functions including anticancer activity. IP6 is converted to inositol di-, tri-, and tetra-phosphates (IP2, IP3, and IP4) by phytase in large intestinal microbes; however, their contribution to the IP6-mediated functions has not been investigated. We have developed the preparations of IP2-4 and IP3rich phytate hydrolysate (IP3-RPH) by IP6 digestion using microbial phytase, and examined the induction of intracellular Ca 21 signaling in response to the preparations in colorectal cancer cells. IP2-4, but not inositol (IP0) and IP6, induced increases in intracellular Ca 21 concentration ([Ca 21 ] i ) in Caco-2 cells with the following rank order: IP34IP2 5 IP4. Inositol tri-phosphate (IP3)-RPH induced increases in [Ca 21 ] i in both undifferentiated Caco-2 and HT-29 cells, but not in differentiated Caco-2. The IP3-RPH-induced [Ca 21 ] i increase was resistant to extracellular Ca 21 depletion, however, it was impaired by inhibitors of phospholipase C, inositol 1, 4, 5 tri-phosphate receptor, ryanodine receptor, and Gaq protein. These results show that the putative G protein-coupled receptor on the plasma membrane senses the IP6 hydrolysates and activates phospholipase Cb, resulting in Ca 21 mobilization through Ca 21 channels coupled with the inositol 1, 4, 5 tri-phosphate and ryanodine receptors on the sarco-endoplasmic reticulum Ca 21 store in colorectal cancer cells.