Journal
CANCER LETTERS
Volume 160, Issue 1, Pages 21-28Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0304-3835(00)00549-8
Keywords
grapefruit juice; orange juice; methoxyflavone; vincristine; multidrug resistance; cancer chemotherapy
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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 [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 increased the uptake of [H-3]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 [H-3]vincristine, resulting in the intracellular accumulation of chamotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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