Phytochemical regulation of UDP-glucuronosyltransferases: implications for cancer prevention.
Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are Phase II biotransformation enzymes that metabolize endogenous and exogenous compounds, some of which have been associated with cancer risk. Many phytochemicals have been shown to induce UGTs in humans, rodents, and cell culture systems. Because UGTs maintain hormone balance and facilitate excretion of potentially carcinogenic compounds, regulation of their expression and activity may affect cancer risk. Phytochemicals regulate transcription factors such as the nuclear factor-erythroid 2-related factor 2 (Nrf2), aryl hydrocarbon, and pregnane X receptors as well as proteins in several signal transduction cascades that converge on Nrf2 to stimulate UGT expression. This induction can be modified by several factors, including phytochemical dose and bioavailability and interindividual variation in enzyme expression. In this review, we summarize the knowledge of dietary modulation of UGTs, particularly by phytochemicals, and discuss the potential mechanisms by which phytochemicals regulate UGT transcription.
Saracino
Misty R
MR
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Lampe
Johanna W
JW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D028321:Plant Preparations / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D020536:Enzyme Activators; D051267:NF-E2-Related Factor 2; D028321:Plant Preparations; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid; D014453:Glucuronosyltransferase