Dual action of cyclin-dependent kinase inhibitors: induction of cell cycle arrest and apoptosis. A comparison of the effects exerted by roscovitine and cisplatin.

作者: Marcel Horky , Jozefa Wesierska-Gadek , Marieta Gueorguieva

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摘要: Cyclin-dependent kinases (CDKs) have recently raised considerable interest in view of their key role the regulation cell cycle progression. In proliferating cells, distinct CDKs associated with specific cyclins coordinate an orchestrated way appropriate transition between different phases cycle. Mutations and/or aberrant expression and regulatory components lead to uncontrolled proliferation finally carcinogenesis. However, post-mitotic neurons, all exception CDK5 are silent. CDK5, a proline-directed serine/ threonine kinase exhibiting close structural homology mitotic CDKs, binds p35, neuron-specific subunit CDK5. is very abundant mature neurons seems regulate neurotransmitter release through phosphorylation down-regulation calcium channel activity. Therefore, inhibition after oxidative stress neurodegenerative disorders has protective action. Selective inhibitors were developed as promising drugs for cancer therapy due ability arrest The aim this study was compare anti-proliferative effect roscovitine (ROSC), potent inhibitor, that cisplatin (CP) on human breast MCF-7 cells. ROSC exerted stronger inhibitory progression than CP. Accumulation G 2 /M arrested cells starting 6 h onset treatment coincided strong upregulation p53. Reconstitution caspase-3 sensitized CP It implicates inhibits more selectively efficaciously carcinoma

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