Pedro Gonçalves and Fátima Martel Pages 994 - 1008 ( 15 )
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.
Absorption, BCRP, butyrate, colorectal cancer, dietary fiber, MCT1, SMCT1, xenobiotics.
Department of Biochemistry, Faculty of Medicine of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.