Staurosporine reduces P-glycoprotein expression and modulates multidrug resistance.
We have investigated the effect of staurosporine and other kinase inhibitors on the mRNA and protein levels of the P-glycoprotein (P-gp) in multidrug resistant (MDR) cells. Treatment of human MDR KB-V1 cells with staurosporine for 24 h caused up to a 50% decrease in the amount of P-gp mRNA and protein present. Co-treatment of KB-V1 cells with verapamil, a known reversal agent, plus staurosporine, H-9, or K252a resulted in an enhanced sensitization of cells to vinblastine than with verapamil alone. These findings support a role for protein kinases in the control of multidrug resistance through effects on P-gp levels.
Sampson
K E
KE
Cell Biology Department, Upjohn Company, Kalamazoo, Michigan 49001.
Wolf
C L
CL
Abraham
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I
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000494:pharmacology; D007624:KB Cells; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000235:genetics; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D019311:Staurosporine; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000970:Antineoplastic Agents; D002227:Carbazoles; D026121:Indole Alkaloids; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D014700:Verapamil; D011494:Protein Kinases; D019311:Staurosporine