Coffee Reduces <i>SULT1E1</i> Expression in Human Colon Carcinoma Caco-2 Cells

Abstract

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 for the preventive action of coffee, we investigated the effect of coffee on estrogen sulfotransferase (SULT) because sulfation is the major pathway involved in the inactivation of estrogens. We found that coffee reduced SULT1E1 gene expression in human colon carcinoma Caco-2 cells. Treatment with 2.5% (v/v) coffee for 24 h resulted in a 60% reduction of the expression of the SULT1E1 gene in Caco-2 cells. Corresponding to reduced SULT1E1 gene expression, cytosolic estrogen SULT activity toward E(2) (20 nM) decreased by 25%. In addition, an accumulation of E(2) sulfates in the medium, which reflects cellular activity of estrogen SULT, decreased after the cells were treated with coffee. Major bioactive constituents in coffee such as caffeine, chlorogenic acid and caffeic acid did not show any effect. The inhibitory activity was extractable by using ethyl acetate. We also found that the inhibitory activity was produced by roasting the coffee beans. Mithramycin, an inhibitor of the transcription factor stimulating protein 1 (Sp1), was able to restore coffee-reduced SULT1E1 gene expression. Our data suggest that daily coffee consumption may reduce estrogen SULT activity, thereby enhancing estrogenic activity in the colon.

Prospective study of breast cancer in relation to coffee, tea and caffeine in Sweden

“…In vitro studies found that coffee reduced the phase II enzyme, estrogen sulfotransferases (SULT1E1) gene expression in Caco‐2 cells. Because sulfation is the major pathway involved in the inactivation of estrogens, the effect on SULT1E1 may enhance estrogen activity and thereby explain why the inverse association between coffee and cancer risk is more evident among subgroups of postmenopausal women for some cancers …”

“…Because sulfation is the major pathway involved in the inactivation of estrogens, the effect on SULT1E1 may enhance estrogen activity and thereby explain why the inverse association between coffee and cancer risk is more evident among subgroups of postmenopausal women for some cancers. 29 A number of epidemiologic studies have estimated the association between coffee consumption and the risk of breast cancer, but the results were inconclusive. Several case- 1 One cup of coffee 5 150 ml.…”

The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression

“…Previous studies revealed that coffee consumption had the chemopreventive effect in colorectal cancer, and several bioactive compounds showed the pharmacological effectiveness ( Vitaglione et al ., 2012 ; Isshiki et al ., 2013 ). The present study demonstrated that kahweol, the coffee deterpene, significantly suppressed the viability of HT-29 human colorectal cancer cells.…”

Coffee and cancer risk, epidemiological evidence, and molecular mechanisms

“…In vitro studies found that coffee reduced the phase II enzyme, estrogen sulfotransferases (SULT1E1) gene expression in Caco‐2 cells with 60%. Because sulfation is the major pathway involved in the inactivation of estrogens, the effect on SULTE1 may enhance estrogen activity and thereby explain why the inverse association between coffee and cancer risk is more evident among subgroups of postmenopausal women for some cancers . The responsible bioactive constituents for the SULTE inhibition were produced under the roasting process.…”