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 journalArticlepeer-review

97 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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