title: The influence of curcumin, quercetin, and eicosapentaenoic acid on the expression of phase II detoxification enzymes in the intestinal cell lines HT-29, Caco-2, HuTu 80, and LT97.
abstract: Curcumin, quercetin, and eicosapentaenoic acid (EPA) are 3 natural compounds with the capacity to reduce adenoma burden in patients with familial adenomatous polyposis (FAP). The mechanistic basis of this anticarcinogenic capacity is largely unknown, but it was suggested that induction of detoxification enzymes is involved. Therefore, the effects of low-dose curcumin, quercetin, and EPA on phase II detoxification enzymes UDP-glucuronosyltransferase (UGT), glutathione S-transferase (GST), as well as on glutathione (GSH) content were analyzed in 4 cell line models of intestinal carcinogenesis. HT-29, HuTu 80, and Caco-2 intestinal cancer cells and LT97 colon adenoma cells from a patient with FAP were treated with low-dose noncytotoxic concentrations of curcumin, quercetin, and EPA. GST enzyme activity was measured by spectrophotometry, and expression of GSTA1, GSTM1, GSTP1, GSTT1, and UGT1 by Western blotting. Cytosolic GSH levels were determined by high performance liquid chromatography. An inducing effect of curcumin and quercetin on GST or UGT was seen in Caco-2, LT97, and HuTu 80 cells. GSH levels were reduced by quercetin and EPA in HT-29 cells and induced by curcumin in Caco-2 cells. In LT97 cells, GST activity and expression was reduced, but UGT1 expression was induced by curcumin and quercetin; whereas EPA only decreased GST or UGT levels. In summary, enhancement of the detoxification capacity by low dose of the potential anticarcinogens curcumin, quercetin, or EPA seems only a minor factor in explaining their anticarcinogenic properties.
authors: Department of Gastroenterology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Julia
authors: J
authors: Odenthal
authors: Bjorn W H
authors: BW
authors: van Heumen
authors: Hennie M J
authors: HM
authors: Roelofs
authors: Rene H M
authors: RH
authors: te Morsche
authors: Brigitte
authors: B
authors: Marian
authors: Fokko M
authors: FM
authors: Nagengast
authors: Wilbert H M
authors: WH
authors: Peters
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018938:Caco-2 Cells; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D050217:Metabolic Detoxication, Phase II; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D011794:Quercetin; D015118:Eicosapentaenoic Acid; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D003474:Curcumin