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

• Published in: Cancer letters Vol. 177; no. 1; pp. 89 - 93
• Main Authors: Ikegawa, Tomomi, Ohtani, Hisakazu, Koyabu, Noriko, Juichi, Motoharu, Iwase, Yukiko, Ito, Chihiro, Furukawa, Hiroshi, Naito, Mikihiko, Tsuruo, Takashi, Sawada, Yasufumi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 08.03.2002; Elsevier; Elsevier Limited
• Subjects: Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B - metabolism; Biological and medical sciences; Cancer; Cell culture; Chemotherapy; Derivatives; Dose-Response Relationship, Drug; Doxorubicin - pharmacology; Drug Resistance, Neoplasm; Flavonoid derivatives; Flavonoids - pharmacology; Humans; K562 Cells - drug effects; K562 Cells - metabolism; Medical sciences; Multidrug resistance; P-glycoprotein; Pharmacology. Drug treatments; Proteins; Quercetin - pharmacology; Tumors; Vincristine; Vincristine - pharmacology; Japan; P-glycoprotein; Flavonoid derivatives; Vincristine; Multidrug resistance; Antineoplastic agent; Human; Leukemia; P Glycoprotein; Malignant hemopathy; Anticarcinogen; Antitumor promotor; Doxorubicin; Flavonoid; In vitro; Biological activity; Resistance; Multiple resistance; Plant origin; Anthracyclins; Mechanism of action; Tumor cell
• DOI: 10.1016/S0304-3835(01)00761-3
• ISSN: 0304-3835

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.