TY - JOUR
T1 - Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells
AU - Ikegawa, Tomomi
AU - Ohtani, Hisakazu
AU - Koyabu, Noriko
AU - Juichi, Motoharu
AU - Iwase, Yukiko
AU - Ito, Chihiro
AU - Furukawa, Hiroshi
AU - Naito, Mikihiko
AU - Tsuruo, Takashi
AU - Sawada, Yasufumi
PY - 2002/3/8
Y1 - 2002/3/8
N2 - 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.
AB - 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.
KW - Flavonoid derivatives
KW - Multidrug resistance
KW - P-glycoprotein
KW - Vincristine
UR - http://www.scopus.com/inward/record.url?scp=18244403795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18244403795&partnerID=8YFLogxK
U2 - 10.1016/S0304-3835(01)00761-3
DO - 10.1016/S0304-3835(01)00761-3
M3 - Article
C2 - 11809535
AN - SCOPUS:18244403795
SN - 0304-3835
VL - 177
SP - 89
EP - 93
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
