Overview
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Alomone Labs Roscovitine prevents NGF-mediated survival of PC-12 cells.Cells were grown in the absence of serum. The cells were not protected (dotted line) or protected (continuous line) from apoptosis with 100 ng/ml Native mouse NGF 2.5S protein (99%) (#N-240) and treated with different concentrations of Roscovitine (#R-300). Cell survival was measured after 4 days using the XTT method, calculated as a relative percentage of the control without Roscovitine and plotted against Roscovitine concentrations. The basal level of survival without NGF is represented by the gray column.
Roscovitine is an olomoucine-related purine flavopiridol, and is a highly potent inhibitor for the kinase activity of CDK1, CDK2, CDK5, and CDK7 (IC50 ~ 0.5- 0.2 µM) but is a poor inhibitor for CDK 4 and CDK 6 (IC50 > 100 µM). 1-2
Roscovitine inhibits the kinase activity by competing with ATP at the ATP binding site of the kinase.3 Roscovitine concentrations at micromolar levels prevents the cell cycle progression of mammalian cells at the G1-S and G2-M checkpoints by inhibiting DNA synthesis. Moreover, it was found to act as an antiproliferative and antitumoral agent, causing DNA fragmentation, which leads to apoptosis in some human cancer cells.1,3-7
Roscovitine induces activation, stabilization and accumulation of p53 in the nucleus via suppression of MDM2 expression and is independent of CDK2 dependent mechanism.4,6,8
In addition, Roscovitine prevents viral transcription equivalent to the activity of alpha interferon.9 At high concentration levels (EC50 ~ 53 µM) Roscovitine acts to slow the deactivation of N-type Ca2+ channels (CaV2.2).10
Roscovitine was also shown to block CaV3.1 channel currents heterologously expressed in HEK 293 cells.11
