Effects of Coffee on Estrogen Sulfation in Human Colon Carcinoma Caco-2 Cells

Recent epidemiological studies have shown that moderate coffee consumption is associated with a lower risk of certain types of cancers, particularly colon cancer in postmenopausal women. To elucidate the molecular basis of the preventive action of coffee toward colon cancer, we focused on the effects of coffee on the metabolism of estrogens by sulfation, a reaction that inactivates estrogens. Estrogens are sulfonated by estrogen sulfotransferase (SULT1E1), and the sulfonated estrogens are reversely hydrolyzed by steroid sulfatase (STS). Sulfonated estrogens are pumped out of the cells by an ABC transporter, breast cancer resistance protein (BCRP). Intracellular concentrations of active estrogens may be determined by the balance of these activities. In human colon cancer Caco-2 cells, coffee decreases the expression of SULT1E1 and STS, whereas it increases BCRP expression. Activities of these three proteins change according to the expression level of each gene. Active constituents of coffee extract can be generated during the roasting process of coffee beans at different times. Modulation of the expression of these genes is likely to be mediated via activation of transcription factors such as NFκB (. BCRP) and stimulating protein 1 (. SULT1E1). These results suggest that coffee consumption may modulate the inactivation of estrogens by sulfation in human colon cells.