Modulators of the multidrug-transporter, P-glycoprotein, exist in the human plasma.
P-glycoprotein (P-gp) is thought to mediate the transport of anticancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, colon and capillary endothelium of the brain. However, the function and transporting substrates of P-gp in normal tissues are still not understood. This paper explains that some compounds in the human plasma can modulate the transporting activity of P-gp. A partially purified fraction from the human plasma enhanced the accumulation of anti-cancer agents in MDR cells. This fraction inhibited the efflux of vinblastine from MDR cells, and also inhibited the photoaffinity labeling of P-gp with azidopine as effectively as vinblastine, quinidine and cepharanthine. The compounds in this purified fraction may be physiological substrates of P-gp and can probably overcome MDR.
Ichikawa
M
M
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
Yoshimura
A
A
Furukawa
T
T
Sumizawa
T
T
Akiyama
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels / Q000378:metabolism; D001386:Azides / Q000378:metabolism; D001692:Biological Transport; D001798:Blood Proteins / Q000302:isolation & purification / Q000502:physiology*; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides; D001798:Blood Proteins; D004095:Dihydropyridines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D014747:Vinblastine; C041130:azidopine; D003630:Daunorubicin