Smoking and nicotine alter UGT1A expression

Abstract

The expression and activity of enzymes taking role in drug metabolism are important as in the case of phase II glucuronidation enzymes; namely UDPglucuronosyltransferases (UGTs). Previously, it has been identified that smoking upregulates the expression of UGT enzymes in oral mucosa. We asked whether smoking induces UGT1A expression in other tissues and re-analyzed publically available datasets run with samples from smokers and non-smokers. It was observed that UGT1A enzymes were overexpressed in several types of epithelial cells of smokers. 30% of nicotine metabolism is performed by UGT enzymes; however, whether UGT1A expression is modulated by nicotine, the addictive component of tobacco smoke, is not known. For this purpose, the expression levels of UGT1A isoforms were measured using Real-Time PCR in nicotine treated SW620 colorectal cancer cells. Our findings showed that nicotine’s effect on UGT1A expression was isoform specific; and the magnitude of modulation differed among isoforms. Furthermore, the upregulation of UGT1A enzymes could only be observed in serum-deprived SW620 cells. In summary, nicotine metabolism enzymes are regulated by both smoking in vivo and nicotine in vitro. Nevertheless, enhanced xenobiotic metabolism may result in chemoresistance, which is undesirable for cancer patients. Therefore, before drug therapy cancer patients might be analyzed in terms of their smoking status and UGT1A expression patterns.