Dual action of cyclin-dependent kinase inhibitors: induction of cell cycle arrest and apoptosis. A comparison of the effects exerted by @entity9363 and XXXX .

@entity1 @entity22446 @entity0 @entity522 @entity5 @entity900 @entity876 @entity9363 @entity22445 @entity179 @entity460 @entity563 @entity1521 @entity1889 @entity105
Cyclin-dependent kinases (CDKs) have recently raised considerable interest in view of their key role in the regulation of the cell cycle progression. In proliferating cells, distinct CDKs associated with specific cyclins coordinate in an orchestrated way the appropriate transition between different phases of the cell cycle. Mutations and/or aberrant expression of distinct CDKs and their regulatory components lead to uncontrolled proliferation and finally to @entity105 . However, in post-mitotic neurons, all CDKs with the exception of @entity22445 are silent. @entity22445 , a @entity1521 -directed @entity563 / @entity1889 kinase exhibiting a close structural homology to the mitotic CDKs, binds to @entity22446 , the neuron-specific regulatory subunit of @entity22445 . @entity22445 is very abundant in mature neurons and seems to regulate neurotransmitter release through phosphorylation and down-regulation of @entity460 channel activity. Therefore, the inhibition of CDKs in neurons after oxidative stress and in @entity179 has a protective action. Selective CDKs inhibitors were developed as promising drugs for @entity5 therapy due to their ability to arrest cell cycle progression. The aim of this study was to compare the anti-proliferative effect of @entity9363 (ROSC), a potent CDKs inhibitor, with that of @entity900 (CP) on @entity1 @entity0 MCF-7 cells. ROSC exerted stronger inhibitory effect on proliferation and cell cycle progression of MCF-7 than CP. Accumulation of G(2)/M arrested cells starting 6 h after onset of ROSC treatment coincided with a strong up-regulation of the @entity876 . Reconstitution with @entity522 sensitized MCF-7 cells to CP action. It implicates that ROSC inhibits more selectively and efficaciously the proliferation of @entity1 @entity0 cells.
