Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells

Tomomi Ikegawa, Hisakazu Ohtani, Noriko Koyabu, Motoharu Juichi, Yukiko Iwase, Chihiro Ito, Hiroshi Furukawa, Mikihiko Naito, Takashi Tsuruo, Yasufumi Sawada

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55 Citations (Scopus)

Abstract

We investigated the effects of natural flavones, quercetin and morin, and their pentamethyl, pentaethyl, pentapropyl, pentabutyl and pentaallyl ethers, on the function of P-glycoprotein (P-gp) assessed by an increase in the uptake of [3H]vincristine by human myelogenous leukemia (K562) cells and adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Pentamethyl, pentaethyl, pentapropyl and pentaallyl ethers of morin and quercetin (20 μM) all increased the uptake of [3H]vincristine by K562/ADM cells, while quercetin, morin and their pentabutyl ethers had no effect. Pentamethylquercetin, pentaallylquercetin and pentaethylmorin remarkably increased the uptake of [3H]vincristine by K562/ADM cells by 10.6, 10.8 and 14.4-fold, respectively. These inhibitory potencies for P-gp were more potent than typical P-gp inhibitors, cyclosporine A and verapamil. Taking into consideration that these flavonoid derivatives possess antitumor promoter activity, they may become candidates of effective multidrug resistance-reversing agents in cancer chemotherapy.

Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalCancer Letters
Volume177
Issue number1
DOIs
Publication statusPublished - 2002 Mar 8
Externally publishedYes

Keywords

  • Flavonoid derivatives
  • Multidrug resistance
  • P-glycoprotein
  • Vincristine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ikegawa, T., Ohtani, H., Koyabu, N., Juichi, M., Iwase, Y., Ito, C., Furukawa, H., Naito, M., Tsuruo, T., & Sawada, Y. (2002). Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Letters, 177(1), 89-93. https://doi.org/10.1016/S0304-3835(01)00761-3