Adriamycin activates c-jun N-terminal kinase in human leukemia cells: a relevance to apoptosis.
We studied the activation of c-jun N-terminal kinase 1 (JNK 1) and extracellular signal-regulated kinases 1 and 2 (ERK 1/2) of mitogen-activated protein kinase (MAPK) family by adriamycin (ADR) in the human T cell leukemia line, H9. ADR caused an elevation of JNK1 activity at sublethal or lethal concentrations; however, at lower doses, ADR did not activate JNK1. The induction of JNK1 peaked at 4 h of treatment (about ten-fold over the control), and was sustained up to 5 h post-treatment. This induction preceded the onset of apoptosis, as determined by morphological features and internucleosomal degradation of DNA. Upon treatment of cells with JNK1-inducing doses, ADR caused an elevation of steady-state levels of c-jun and ATF3 mRNAs, as measured by RT-PCR. In contrast, the activity of ERK 1/2 remained unchanged throughout the treatments, indicating that members of MAPK family are differentially regulated in ADR-treated cells. A possible role of JNK1 activation in ADR-induced apoptosis is discussed.
Department of Pharmaceutics and Pharmacodynamics, College of Pharmacy, University of Illinois at Chicago 60607, USA.
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Yu
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Shtil
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Tan
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Roninson
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Kong
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D015458:Leukemia, T-Cell / Q000201:enzymology* / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases