Polyunsaturated fatty acids inhibit PI3K activity in a yeast-based model system.

International audienceThe PI3K (phosphatidyl inositol 3' kinase) pathway controls the regulation of cell growth, proliferation, migration and apoptosis. In many tumors, the PI3K gene is mutated or overexpressed, and/or the PI3K pathway is hyperactive. PI3K is therefore a potential pharmacological target for the development of anti-tumor drugs. Some polyunsaturated fatty acids (PUFA), when given in the diet, may lead to a decrease in PI3K activity. We used a yeast-based model to reconstitute the PI3K/PTEN/Akt pathway to study the effects of long chain n-3 fatty acids on PI3K kinase and found that various PUFA were able to alleviate toxicity induced by overexpression of PI3K. The various PUFA had no significant effect on the steady-state level of PI3K catalytic subunit proteins in yeast. However, depletion of PIP2 due to overexpression of the p110α subunit was significantly reduced by treating the yeast cells with the various PUFA. The inhibition of mammalian PI3K, expressed in an exogenous cellular context in yeast, is likely to be a direct effect of these PUFA on PI3K rather than on other mammalian endogenous or environmental factors. These results are particularly promising given the abundance of active PUFA in marine foodstuffs and especially fish oils

Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide

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