Department of Biochemistry, Faculty of Medicine of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Curr Drug Metab. 2013 Nov;14(9):994-1008. doi: 10.2174/1389200211314090006.
Colorectal cancer (CRC) is one of the most common solid tumors worldwide. A diet rich in dietary fiber is associated with a reduction in its risk. Butyrate (BT) is one of the main end products of anaerobic bacterial fermentation of dietary fiber in the human colon. This short-chain fatty acid is an important metabolic substrate in normal colonic epithelial cells and has important homeostatic functions at this level, including the ability to prevent/inhibit carcinogenesis. BT is transported into colonic epithelial cells by two specific carrier-mediated transport systems, the monocarboxylate transporter 1 (MCT1) and the sodium-coupled monocarboxylate transporter 1 (SMCT1). In normal colonic epithelial cells, BT is the main energy source for normal colonocytes and it is effluxed by BCRP. Colonic epithelial tumoral cells show a reduction in BT uptake (through a reduction in MCT1 and SMCT1 protein expression), an increase in the rate of glucose uptake and glycolysis becomes their primary energy source. BT presents an anticarcinogenic effect (induction of cell differentiation and apoptosis and inhibition of cell proliferation) but has an apparent opposing effect upon growth of normal colonocytes (the "BT paradox"). Because the cellular effects of BT (e.g. inhibition of histone deacetylases) are dependent on its intracellular concentration, knowledge on the mechanisms involved in BT membrane transport and its regulation seem particularly relevant in the context of the physiological and pharmacological benefits of this compound. This review discusses the mechanisms of BT transport and integrates this knowledge with the effects of BT in tumoral and normal colonocytes.
结直肠癌（CRC）是世界上最常见的实体肿瘤之一。富含膳食纤维的饮食与降低其风险有关。丁酸（BT）是膳食纤维在人结肠中厌氧细菌发酵的主要终产物之一。这种短链脂肪酸是正常结肠上皮细胞的重要代谢底物，在该水平上具有重要的体内平衡功能，包括预防/抑制致癌作用的能力。BT 通过两种特定的载体介导转运系统，即单羧酸转运蛋白 1（MCT1）和钠偶联单羧酸转运蛋白 1（SMCT1），被转运到结肠上皮细胞内。在正常结肠上皮细胞中，BT 是正常结肠细胞的主要能量来源，它通过 BCRP 被排出细胞外。结肠上皮肿瘤细胞显示 BT 摄取减少（通过降低 MCT1 和 SMCT1 蛋白表达），葡萄糖摄取率增加，糖酵解成为其主要能量来源。BT 具有抗癌作用（诱导细胞分化和凋亡，抑制细胞增殖），但对正常结肠细胞的生长有明显的拮抗作用（“BT 悖论”）。由于 BT 的细胞效应（例如抑制组蛋白去乙酰化酶）依赖于其细胞内浓度，因此了解 BT 膜转运及其调节的机制在该化合物的生理和药理作用方面似乎特别相关。这篇综述讨论了 BT 转运的机制，并将这些知识与 BT 在肿瘤和正常结肠细胞中的作用相结合。
