Anti-cancer effect by metabolic conversion

将癌细胞独特的代谢从糖酵解转变为葡萄糖氧化会降低细胞的存活率。我们调查了改变支链氨基酸(BCAA)代谢是否也会杀死癌细胞。激活支链氨基酸代谢的中链脂肪酸辛酸酯(C8)可诱导癌细胞死亡，而对正常细胞无影响。我们发现，最有效的MCFA是月桂酸酯(C12)，它对支链氨基酸的代谢没有影响。月桂酸与油酸盐一起处理会显著降低几种癌细胞的存活率。月桂酸能增加对油酸的摄取，增加细胞内过量油酸的摄取，从而通过脂毒应激反应导致细胞死亡，这些反应因细胞类型而异。此外，艾氏腹水瘤小鼠腹腔注射不饱和脂肪酸月桂酸酯可显著抑制腹水在腹水中的蓄积，提高小鼠存活率。这些结果表明，月桂酸酯和不饱和脂肪酸的组合具有很大的抗肿瘤活性。

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.