Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse.
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.
Valentine
Sophie P
SP
Department of Pharmacology and Toxicology, 18 Frederick Street, Adams Building, University of Otago, Dunedin, New Zealand.
Le Nedelec
Martin J
MJ
Menzies
Anna R
AR
Scandlyn
Marissa J
MJ
Goodin
Mette G
MG
Rosengren
Rhonda J
RJ
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
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