TAILIEUCHUNG - Báo cáo khoa học: Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5)

Plant flavonoids are polyphenolic compounds, commonly found in vegeta-bles, fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP-bind-ing cassette transporters that are linked with anticancer and antiviral drug resistance and, as such, may be beneficial in modulating drug resistance. This study investigates the interactions of six common polyphenols; querce-tin, silymarin, resveratrol, naringenin, daidzein and hesperetin with the multidrug-resistance-associated proteins, MRP1, MRP4 and MRP5. . | ềFEBS Journal Modulatory effects of plant phenols on human multidrug-resistance proteins 1 4 and 5 ABCC1 4 and 5 Chung-Pu Wu1 2 Anna Maria Calcagno2 Stephen B. Hladky1 Suresh V. Ambudkar2 and Margery A. Barrand1 1 Department of Pharmacology University of Cambridge UK 2 Laboratory of CellBiology Centre for Cancer Research NationalCancer Institute Bethesda MD USA Keywords ABC transporters drug resistance multidrug-resistant proteins 1 4 and 5 plant polyphenols red blood cells Correspondence S. V. Ambudkar Laboratory of Cell Biology NationalCancer Institute NIH Building 37 Room 2120 37 Convent Drive Bethesda MD 20892-4256 USA Fax 1 301 435 8188 Tel 1 301 402 4178 E-mail ambudkar@ Received 17 June 2005 revised 25 July 2005 accepted 28 July 2005 doi Plant flavonoids are polyphenolic compounds commonly found in vegetables fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP-bind-ing cassette transporters that are linked with anticancer and antiviral drug resistance and as such may be beneficial in modulating drug resistance. This study investigates the interactions of six common polyphenols quercetin silymarin resveratrol naringenin daidzein and hesperetin with the multidrug-resistance-associated proteins MRP1 MRP4 and MRP5. At nontoxic concentrations several of the polyphenols were able to modulate MRP1- MRP4- and MRP5-mediated drug resistance though to varying extents. The polyphenols also reversed resistance to NSC251820 a compound that appears to be a good substrate for MRP4 as predicted by data-mining studies. Furthermore most of the polyphenols showed direct inhibition of MRP1-mediated 3H dinitrophenyl S-glutathione and MRP4-mediated 3H cGMP transport in inside-out vesicles prepared from human erythrocytes. Also both quercetin and silymarin were found to inhibit MRP1- MRP4- and MRP5-mediated transport from intact cells with high affinity.

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