Caffeic acid inhibits the uptake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by inducing the efflux transporters expression in Caco-2 cells.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed as a by-product of the Maillard reaction during cooking and frying of protein-rich foods at high temperatures. PhIP is metabolized in the liver by cytochrome P450 1A1/2 to carcinogenic metabolite N-hydroxy PhIP, which can form DNA adduct. The ATP binding cassette (ABC) transporters, P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) are capable of transporting the food-borne procarcinogen PhIP back to the intestinal lumen. In the present study, the uptake and efflux of PhIP were assessed by determining apparent bidirectional permeability coefficients and efflux ratio. The efflux ratio of PhIP with 10 µM caffeic acid was significantly increased compared with control. The mRNA levels of efflux transporters were measured to evaluate the effect of caffeic acid in the presence of PhIP on efflux-mediated transport of PhIP. Caco-2 cells exposed to 10 µM caffeic acid for 3 and 6 h also exhibited higher mRNA levels of P-gp and BCRP than those of control. In contrast, the mRNA level of MRP2 was only slightly induced after 3 h and 6 h. Therefore, caffeic acid at low concentration is expected to be used not only as an antioxidant, but also as an inhibitor of the absorption of food borne carcinogen heterocyclic amines. However, further studies, especially in vivo studies, are required to confirm these results.
Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University.
Yun-Jin
YJ
Hong
Sung-Yong
SY
Yang
Mi-Hyun
MH
Nam
Yun-Chang
YC
Koo
Kwang-Won
KW
Lee
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002109:Caffeic Acids / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002109:Caffeic Acids; D007093:Imidazoles; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C040048:caffeic acid