Abstract
BMI-1026 is a synthetic aminopyrimidine compound that targets cyclin dependent kinases (cdks) and was initially designed as a potential anticancer drug. Even though it has been well documented that BMI-1026 is a potent cdk inhibitor, little is known about the cellular effects of this compound. In this study, we examined the effects of BMI-1026 treatment on inducing premature senescence and then evaluated the biochemical features of BMI-1026-induced premature senescence. From these experiments we determined that BMI-1026 treatment produced several biochemical features of premature senescence and also stimulated expression of mitogen activated protein kinase (MAPK) family proteins. BMI-1026 treatment caused nuclear translocation of activated Erk1/2 and the formation of senescence associated heterochromatin foci in 5 days. The heterochromatin foci formation was perturbed by inhibition of Erk1/2 activation.
Publication types
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Evaluation Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology
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Caveolin 1 / metabolism
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Cells, Cultured
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Cellular Senescence / drug effects*
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Cellular Senescence / genetics
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Enzyme Inhibitors / pharmacology
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Heterochromatin / chemistry
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Heterochromatin / drug effects*
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Humans
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phenols / adverse effects
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Phenols / pharmacology*
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Phosphorylation / drug effects
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Protein Transport / drug effects
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Pyrimidines / adverse effects
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Pyrimidines / pharmacology*
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Up-Regulation / drug effects
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beta-Galactosidase / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antineoplastic Agents
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BMI 1026
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Caveolin 1
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Enzyme Inhibitors
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Heterochromatin
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Phenols
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Pyrimidines
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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beta-Galactosidase