Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells

We investigated the effects of the ethyl acetate extract of grapefruit juic e (GFJ), that of orange juice (OJ) and their components on the uptake of [H -3]vincristine into adriamycin-resistant human myelogenous leukemia cells. Its uptake was increased by the extracts of GFJ and OJ up to 7- and 3-fold, respectively, as well as verapamil and cyclosporin A. OJ components, i.e. 3,3',4'.5.6,7,8-heptamethoxyflavone, nobiletin and tangeretin, also increas ed the uptake of [H-3]vincristine in a concentration-dependent manner. Alth ough GFJ components, dihydroxybergamottin and bergamottin, significantly in creased the uptake, their potencies were considerably weaker than those of OJ components. These data suggest that OJ components inhibit P-gp-mediated efflux of [H-3]vincristine, resulting in the intracellular accumulation of chamotherapeutic drugs. These components may become candidates of multi-dru g resistance reversing agents in cancer chemotherapy. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.