Kinetic parameters for the uptake of anthracycline by drug-resistant and drug-sensitive K562 cells.
Fluorescence-emission spectra from anthracycline-treated cells suspended in buffer have been used to measure the uptake of three anthracycline derivatives: adriamycin, 4'-O-tetrahydropyranyladriamycin and aclacinomycin in drug-sensitive and drug-resistant K562 cells. The initial rate of uptake and the kinetics of active efflux under the effect of an integral membrane glycoprotein, P-glycoprotein, have been measured as a function of temperature. The activation energies for the passage of the drugs through the plasma membrane have been calculated. In the case of 4'-O-tetrahydropyranyladriamycin, the activation energies for the passive diffusion of the drug equal 45 kJ.mol-1 and 37 kJ.mol-1 for sensitive and resistant cells, respectively. The activation energy for the active efflux of 4'-O-tetrahydropyranyladriamycin equal 25 kJ.mol-1.
Tarasiuk
J
J
Laboratoire de Chimie Bioinorganique, Unité de Formation et de Recherche en Santé, Médecine et Biologie Humaine, Bobigny, France.
Garnier-Suillerot
A
A
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D005454:Fluorescence Polarization; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008560:Membrane Fluidity; D013696:Temperature
C011157:aclacinomycins; D015250:Aclarubicin; D004317:Doxorubicin; C027260:pirarubicin