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Myricetin stimulates the absorption of the pro-carcinogen PhIP

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Author: Schutte, M.E. · Sandt, J.J.M. van de · Alink, G.M. · Groten, J.P. · Rietjens, I.M.C.M.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Cancer Letters, 1, 231, 36-42
Identifier: 239087
doi: doi:10.1016/j.canlet.2005.01.020
Keywords: Biology · Biomedical Research · ABC transporter · Apparent permeability · Caco-2 · Myricetin · PhIP · 2 amino 1 methyl 6 phenylimidazo[4,5 b]pyridine · carcinogen · cyclosporin A · glycoprotein P inhibitor · multidrug resistance protein 2 · myricetin · valspodar · absorption · article · cell differentiation · cell strain CACO 2 · cell transport · concentration (parameters) · excretion · human · human cell · intestine epithelium cell · priority journal · stimulation · Absorption · ATP-Binding Cassette Transporters · Caco-2 Cells · Carcinogens · Flavonoids · Humans · Imidazoles · Membrane Transport Proteins · Multidrug Resistance-Associated Proteins · Permeability

Abstract

The effect of the flavonoid myricetin on the transport of the pro-carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through differentiated Caco-2 monolayers, a model for the intestinal epithelium, is described. Myricetin causes an increase of the transport of PhIP from the apical to the basolateral compartment. This effect was observed at physiologically relevant concentrations of PhIP and myricetin. Cyclosporin A (MRP2 inhibitor) but not PSC833 (P-gp inhibitor) showed a similar effect on PhIP transport. The results indicate that myricetin induces an increased basolateral uptake of the pro-carcinogen PhIP, in part through inhibition of the MRP2 mediated excretion of PhIP from the intestinal cells back to the lumen. © 2005 Elsevier Ireland Ltd. All rights reserved.