Serotonin transporter expression and DNA methylation are altered by coffee exposure in Caco-2 cells

Consumption of coffee is associated with a reduced risk of colorectal cancer (CRC); however, the underlying mechanisms are not fully understood. Gut serotonin (5-HT) plays a complex role in CRC development. Intestinal 5-HT levels are regulated by the serotonin transporter (SERT), in intestinal epithelial cells. Recent evidence suggests a correlation between SERT expression and DNA methylation of a functional CpG site (CpG3) in the promoter region of SLC6A4, the SERT gene. This study investigated the effects of coffee on SERT expression in Caco-2 cells, an intestinal epithelial cell model. Exposure of Caco-2 cells to instant coffee solution 1-10% (v/v) for 48 h was found to result in a concentration-dependent decrease in SERT-mediated 5-HT uptake and SERT mRNA expression. This effect was observed for different instant coffee brands and coffee bean species, and was not reproduced by exposure to major coffee components such as caffeine and chlorogenic acid, or by extracts from unroasted green coffee beans. Pyrosequencing revealed that coffee exposure altered the DNA methylation of CpG3. This preliminary study suggests a novel mechanism by which coffee protects against CRC: suppression of SERT expression in intestinal epithelial cells, possibly via epigenetic modification of SLC6A4.