Sahuri-Arisoylu Meliz, Mould Rhys R, Shinjyo Noriko, Bligh S W Annie, Nunn Alistair V W, Guy Geoffrey W, Thomas Elizabeth Louise, Bell Jimmy D
Research Centre of Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom.
Health Innovation Ecosystem, University of Westminster, London, United Kingdom.
Front Nutr. 2021 Apr 15;8:588466. doi: 10.3389/fnut.2021.588466. eCollection 2021.
Acetate is one of the main short chain fatty acids produced in the colon when fermentable carbohydrates are digested. It has been shown to affect normal metabolism, modulating mitochondrial function, and fatty acid oxidation. Currently, there is no clear consensus regarding the effects of acetate on tumorigenesis and cancer metabolism. Here, we investigate the metabolic effects of acetate on colon cancer. HT29 and HCT116 colon cancer cell lines were treated with acetate and its effect on mitochondrial proliferation, reactive oxygen species, density, permeability transition pore, cellular bioenergetics, gene expression of acetyl-CoA synthetase 1 () and 2 (), and lipid levels were investigated. Acetate was found to reduce proliferation of both cell lines under normoxia as well as reducing glycolysis; it was also found to increase both oxygen consumption and ROS levels. Cell death observed was independent of expression. Under hypoxic conditions, reduced proliferation was maintained in the HT29 cell line but no longer observed in the HCT116 cell line. expression together with cellular lipid levels was increased in both cell lines under hypoxia which may partly protect cells from the anti-proliferative effects of reversed Warburg effect caused by acetate. The findings from this study suggest that effect of acetate on proliferation is a consequence of its impact on mitochondrial metabolism and during normoxia is independent of expression.
乙酸盐是结肠中可发酵碳水化合物消化时产生的主要短链脂肪酸之一。研究表明，它会影响正常代谢，调节线粒体功能和脂肪酸氧化。目前，关于乙酸盐对肿瘤发生和癌症代谢的影响尚无明确共识。在此，我们研究乙酸盐对结肠癌的代谢作用。用乙酸盐处理HT29和HCT116结肠癌细胞系，并研究其对线粒体增殖、活性氧、密度、通透性转换孔、细胞生物能学、乙酰辅酶A合成酶1（ ）和2（ ）的基因表达以及脂质水平的影响。发现乙酸盐在常氧条件下可降低两种细胞系的增殖并减少糖酵解；还发现它会增加氧消耗和活性氧水平。观察到的细胞死亡与 表达无关。在低氧条件下，HT29细胞系的增殖持续降低，但在HCT116细胞系中不再观察到。在低氧条件下，两种细胞系中 表达以及细胞脂质水平均升高，这可能部分保护细胞免受乙酸盐引起的反向Warburg效应的抗增殖作用。本研究结果表明，乙酸盐对增殖的影响是其对线粒体代谢影响的结果，在常氧条件下与 表达无关。
