Myricetin stimulates the absorption of the pro-carcinogen PhIP

Schutte, Maaike E.; van de Sandt, Johannes J.M.; Alink, Gerrit M.; Groten, John P.; Rietjens, Ivonne M.C.M.

doi:10.1016/j.canlet.2005.01.020

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Volume 231, Issue 1 , Pages 36-42, 8 January 2006

Myricetin stimulates the absorption of the pro-carcinogen PhIP

Maaike E. Schutte
- Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
- WU/TNO Center for Food Toxicology, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
- Corresponding author. Address: Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands. Tel.: +31 317 48 2137; fax: +31 317 48 4931.
Johannes J.M. van de Sandt
- TNO Nutrition and Food Research, Physiological Sciences Department, P.O. Box 360, 3700 AJ Zeist, The Netherlands
- WU/TNO Center for Food Toxicology, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
Gerrit M. Alink
- Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
John P. Groten
- TNO Nutrition and Food Research, Physiological Sciences Department, P.O. Box 360, 3700 AJ Zeist, The Netherlands
- WU/TNO Center for Food Toxicology, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
Ivonne M.C.M. Rietjens
- Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands
- WU/TNO Center for Food Toxicology, P.O. Box 8000, 6700 EA Wageningen, The Netherlands

Received 24 September 2004; accepted 14 January 2005.

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.

Keywords: Myricetin, PhIP, Caco-2, ABC transporter, Apparent permeability