Effect of orally administered phenethyl isothiocyanate on hepatic gene expression in rats.
METHODS
Phenethyl isothiocyanate (PEITC) is a constituent of cruciferous vegetables that has demonstrated cancer preventive activity in a number of cancer models including lung, prostate, and breast cancer. Our objective was to examine the effects of the oral administration of PEITC for 7 days on the hepatic expression of genes important in drug metabolism and toxicity in Sprague Dawley rats. The liver is the major site for the metabolism of various xenobiotics and carcinogens, and determining the effects of PEITC on the gene expression of hepatic enzymes may provide insight into mechanisms underlying the cancer preventive activity of PEITC.


RESULTS
Using a microarray containing 282 genes, we observed that PEITC significantly up-regulated UDP-glucuronosyltransferase UGT1A6 and strongly down-regulated nicotinamide N-methyltransferase (NNMT). We also confirmed the down-regulation of NNMT by real-time quantitative RT-PCR. Other genes that were significantly up-regulated were the drug metabolizing enzyme cyp2b15, the anti-apoptotic gene bcl2l2, and the stress regulators Gadd45b, Dnajb9, Dnajb5 and Hspb1.


CONCLUSIONS
Our results indicate new targets that may be important in the mechanisms of the anticancer effects of PEITC. Of particular significance was the down-regulation of NNMT which may represent a new target for the treatment of a variety of cancers.
Telang
Urvi
U
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Morris
Marilyn E
ME
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002273:Carcinogens / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage*; D016014:Linear Models; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate; D050903:Nicotinamide N-Methyltransferase; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase