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 juice (GFJ), that of orange juice (OJ) and their components on the uptake of [(3)H]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 increased the uptake of [(3)H]vincristine in a concentration-dependent manner. Although GFJ components, dihydroxybergamottin and bergamottin, significantly increased the uptake, their potencies were considerably weaker than those of OJ components. These data suggest that OJ components inhibit P-gp-mediated efflux of [(3)H]vincristine, resulting in the intracellular accumulation of chemotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy.