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

Research output: Contribution to journalArticle

54 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

Fingerprint

Myeloid Leukemia
K562 Cells
P-Glycoprotein
Flavonoids
Doxorubicin
Ethers
Quercetin
Vincristine
Flavones
Multiple Drug Resistance
Verapamil
Antineoplastic Agents
Cyclosporine
morin

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. / Ikegawa, Tomomi; Ohtani, Hisakazu; Koyabu, Noriko; Juichi, Motoharu; Iwase, Yukiko; Ito, Chihiro; Furukawa, Hiroshi; Naito, Mikihiko; Tsuruo, Takashi; Sawada, Yasufumi.

In: Cancer Letters, Vol. 177, No. 1, 08.03.2002, p. 89-93.

Research output: Contribution to journalArticle

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, vol. 177, no. 1, pp. 89-93. https://doi.org/10.1016/S0304-3835(01)00761-3
Ikegawa, Tomomi ; Ohtani, Hisakazu ; Koyabu, Noriko ; Juichi, Motoharu ; Iwase, Yukiko ; Ito, Chihiro ; Furukawa, Hiroshi ; Naito, Mikihiko ; Tsuruo, Takashi ; Sawada, Yasufumi. / Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. In: Cancer Letters. 2002 ; Vol. 177, No. 1. pp. 89-93.
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