Genistein induction of human sulfotransferases in HepG2 and Caco-2 cells.
Sulfotransferases are phase II drug-metabolizing enzymes. While the induction of sulfotransferases by hormones and endogenous molecules is relatively well known, induction by xenobiotics is not well studied. Isoflavones are naturally occurring phyto-oestrogens, mainly existing in soy food products. They have been described as health-promoting, disease-preventing dietary supplements and as agents with cancer-preventive activities. Recently, isoflavones have been reported to interact with nuclear receptors, including those that are known to mediate the induction of drug-metabolizing enzymes. In the present investigation, the isoflavone genistein was shown to be a xenobiotic inducer of human sulfotransferases in transformed human liver cells (HepG2) and colon carcinoma cells (Caco-2). Enzymatic activity assay, Western blot, and real-time reverse transcription-polymerase chain reaction (RT-PCR) results demonstrated that genistein significantly induced protein and mRNA expression of human simple phenol sulfotransferase (hSULT1A1) and human dehydroepiandrosterone sulfotransferase (hSULT2A1) in HepG2 and Caco-2 cells. The induction was time-dependent and dose-dependent. Western blot results agreed well with real-time RT-PCR results, suggesting that induction occurred at the gene transcription level. This isoflavone is the first nutritionally related phyto-oestrogen shown to induce human sulfotransferases in HepG2 and Caco-2 cells.
Chen
Yue
Y
Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
Huang
Chaoqun
C
Zhou
Tianyan
T
Chen
Guangping
G
D015239:Arylsulfotransferase / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D048789:Phytoestrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000235:genetics
D048789:Phytoestrogens; D012333:RNA, Messenger; D019833:Genistein; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C028152:alcohol sulfotransferase