Coffee reduces SULT1E1 expression 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 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.
Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo 105–8512, Japan.
Marina
M
Isshiki
Haruka
H
Ohta
Hiroomi
H
Tamura
D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D040503:Coffea; D003069:Coffee; D003110:Colonic Neoplasms / Q000201:enzymology; D004958:Estradiol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D008926:Plicamycin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
D003069:Coffee; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts; D011500:Protein Synthesis Inhibitors; D016329:Sp1 Transcription Factor; D004958:Estradiol; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D008926:Plicamycin