In vivo effects of doxorubicin on kinase C in cultured cells.
The ability of doxorubicin to inhibit kinase C in vivo in cultured BALB/c 3T3 mouse fibroblasts was determined by the phosphorylation of the myristoylated alanine-rich C kinase substrate (MARCKS) and the induction of c-fos transcription following treatment with 200 nM phorbol 12-myristate 13-acetate. A concentration of 60 microM doxorubicin did not inhibit MARCKS phosphorylation but completely inhibited c-fos expression. The inhibition of c-fos expression was not specifically mediated via kinase C, since both the total RNA synthesis as measured by [3H]-uridine uptake and the fraction of serum-induced c-fos expression that was not attributable to kinase C were inhibited by doxorubicin. The present data do not support the hypothesis that the cytotoxic effect of doxorubicin is attributable to the inhibition of kinase C in vivo.
Otsuka
M
M
Harbor-UCLA Medical Center, Torrance 90509.
Shigeoka
H
H
Yang
H C
HC
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D012313:RNA; D004317:Doxorubicin; D011493:Protein Kinase C