Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
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Submission date: 2016-09-27
Final revision date: 2017-01-06
Acceptance date: 2017-01-12
Online publication date: 2018-07-05
Publication date: 2018-10-31
Arch Med Sci 2018;14(6):1281-1288
Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP6) is enriched in rice bran and possesses many beneficial effects. Mammalian target of rapamycin (mTOR) is a vital signaling pathway involved in many cellular processes. Inhibition of the mTOR pathway leads to the activation of autophagy-mediated cell death. Autophagy is a cell survival process as well as a cell death mechanism and is a response to various anticancer therapies in cancer cell types. We studied the effect of IP6 on autophagy-mediated death in HT-29 colon cancer cells.

Material and methods:
Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining.

Incubation of cells with IP6 resulted in downregulation of the p-Akt and mTOR pathway in a time-dependent manner. Inositol-6 phosphate (10 µg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP6. Furthermore, IP6 induced apoptosis, as revealed by annexin V staining.

Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway.

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