Staurosporine, a potent inhibitor of C-kinase, enhances drug accumulation in multidrug-resistant cells.
Staurosporine, a potent inhibitor of C-kinase, enhances accumulation of vincristine (VCR) in multidrug-resistant cells. We investigated this enhancement by two methods: (I) ATP-dependent VCR binding system; (II) azidopine photolabeling system. The ATP-dependent VCR binding to the resistant cell membrane was inhibited more efficiently by staurosporine than by verapamil. Staurosporine also inhibited the azidopine photolabeling of P-glycoprotein. These results indicate that staurosporine, an inhibitor of C-kinase, might directly bind to P-glycoprotein as well as antitumor agents and Ca2+ channel blockers. These findings also indicate that C-kinase might be involved in the function of P-glycoprotein.
Sato
W
W
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Yusa
K
K
Naito
M
M
Tsuruo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism; D001386:Azides / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004095:Dihydropyridines / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D019311:Staurosporine; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000970:Antineoplastic Agents; D001386:Azides; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008562:Membrane Glycoproteins; D014750:Vincristine; C041130:azidopine; D011494:Protein Kinases; D019311:Staurosporine