Reversal of multidrug resistance by kopsiflorine isolated from Kopsia dasyrachis.
Kopsiflorine, an indole alkaloid of the aspidofractinine-type isolated from Kopsia dasyrachis, was examined for its effect in enhancing drug cytotoxicity in multidrug-resistant tumor cells. The cytotoxicity of vincristine was enhanced in a concentration-dependent manner by kopsiflorine in drug-resistant KB cells (VJ-300). Kopsiflorine alone had no effect on the growth of drug sensitive or resistant cells, but the intracellular accumulation of vincristine was enhanced by kopsiflorine in VJ-300 cells. Kopsiflorine (10 micrograms/ml) significantly inhibited the binding of [3H]azidopine to P-glycoprotein in VJ-300 cells. The results suggest that kopsiflorine interacts directly with P-glycoprotein and inhibits the efflux of antitumor agents in drug-resistant cells.
Rho
M C
MC
Kitasato Institute, Tokyo, Japan.
Toyoshima
M
M
Hayashi
M
M
Koyano
T
T
Subramaniam
G
G
Kam
T S
TS
Komiyama
K
K
D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology*; D007212:Indolizines / Q000302:isolation & purification / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D007211:Indoles; D007212:Indolizines; C119815:kopsiflorine