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

Tomomi Ikegawa, Fumihiko Ushigome, Noriko Koyabu, Satoshi Morimoto, Yukihiro Shoyama, Mikihiko Naito, Takashi Tsuruo, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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 [3H]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 [3H]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 [3H]vincristine, resulting in the intracellular accumulation of chemotherapeutic drugs. These components may become candidates of multi-drug resistance reversing agents in cancer chemotherapy. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalCancer Letters
Volume160
Issue number1
DOIs
Publication statusPublished - 2000 Nov 10
Externally publishedYes

Keywords

  • Cancer chemotherapy
  • Grapefruit juice
  • Methoxyflavone
  • Multidrug resistance
  • Orange juice
  • Vincristine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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