title: Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse.
abstract: Curcumin, the yellow pigment found in turmeric, exhibits potent chemopreventative properties in both in vivo and in vitro cancer models. We hypothesized that this effect may occur via curcumin-mediated changes in enzymes involved in both carcinogen bioactivation and estrogen metabolism. Female Swiss Webster mice were treated with either curcumin (200 mg/kg or 400 mg/kg, p.o.) or vehicle control for 1 or 2 weeks. The results demonstrated that curcumin had no effect on the catalytic activities of ovarian aromatase, hepatic catechol-O-methyltransferase or hepatic UDP-glucuronosyltransferase. However, both doses of curcumin caused a 25% decrease in CYP1A catalytic activity, but not polypeptide levels, following 2 weeks of treatment. Additionally, following 2 weeks of curcumin at 400 mg/kg, there was a 20% decrease in the catalytic activity and a 28% decrease in polypeptide levels of CYP3A. While 2 weeks of curcumin treatment (400 mg/kg) caused a 20% increase in glutathione S-transferase activity, there was no parallel increase in hepatic stores of the co-factor glutathione. In conclusion small changes in CYP1A, CYP3A and GST following long term treatment (2 weeks) suggest that the combination of all three metabolic pathways may play a small role in curcumin's chemopreventative action.
authors.affiliation: Department of Pharmacology and Toxicology, 18 Frederick Street, Adams Building, University of Otago, Dunedin, New Zealand.
authors.forename: Sophie P
authors.initials: SP
authors.lastname: Valentine
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Le Nedelec
authors.forename: Anna R
authors.initials: AR
authors.lastname: Menzies
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Scandlyn
authors.forename: Mette G
authors.initials: MG
authors.lastname: Goodin
authors.forename: Rhonda J
authors.initials: RJ
authors.lastname: Rosengren
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology; D003474:Curcumin / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D004967:Estrogens; D004364:Pharmaceutical Preparations; D017382:Reactive Oxygen Species; D019392:Cytochrome P-450 CYP2E1; D001141:Aromatase; D051544:Cytochrome P-450 CYP3A; D002394:Catechol O-Methyltransferase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D003474:Curcumin