Anti-cancer effect by metabolic conversion

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Shifting unique metabolism in cancer cells from glycolysis to glucose oxidation can decrease their cell viabilities. We investigated whether altering branched-chain amino acid (BCAA) metabolism also killed cancer cells. Medium-chain fatty acid, caprylate (C8) which activates BCAA metabolism induced cell death of cancer cells with no effect on normal cells. We found that the most effective MCFA was laurate (C12) which had no effect on BCAA metabolism. The treatment of laurate with oleate dramatically decreased the cell viabilities of several cancer cells. Laurate increased the uptake of oleate and the excess amount of intracellular oleate that induce cell death by lipotoxic stress response, which vary by cell type. Moreover, intraperitoneal administration of laurate with unsaturated fatty acid to Ehrich ascite tumor-bearing mice significantly inhibited the accumulation of ascitic fluid in the peritoneal cavities and increased the survival rate of mice. These results suggest that the combination of laurate and unsaturated fatty acid has a great potential for the anti-tumor activity.