Grape seed extract upregulates @entity994 ( @entity994 ) through redox-mediated activation of XXXX and posttranscriptional regulation leading to cell cycle arrest in @entity694 HT29 cells.

@entity1 @entity1366 @entity5 @entity2041 @entity3962 @entity898 @entity2722 @entity694 @entity23886 @entity994
Abnormalities in cell cycle progression provide unlimited replicative potential to @entity5 cells, and therefore targeting of key cell cycle regulators could be a sound @entity5 chemopreventive strategy. Earlier, we found that @entity2722 ( @entity2722 ) increases @entity23886 / @entity994 protein level and inhibits growth and induces apoptosis in @entity1 @entity694 HT29 cells both in vitro and in vivo. However, the mechanism of @entity2722 -induced @entity994 upregulation and its role in biological efficacy of @entity2722 are not known, which were investigated here. @entity2722 treatment of HT29 cells resulted in a strong dose- and time-dependent phosphorylation of @entity3962 ( @entity1366 ), consistent with @entity994 induction. The inhibition of sustained @entity1366 activation by @entity2722 using pharmacological inhibitors abrogated @entity2722 -induced @entity994 upregulation. Furthermore, pretreatment of cells with @entity898 inhibited @entity2722 -induced @entity1366 phosphorylation as well as @entity994 upregulation, suggesting the involvement of @entity2722 -induced oxidative stress as an upstream event. Consistent with this, @entity2722 also decreased intracellular level of reduced @entity2041 . Next, we determined whether @entity2722 -induced signaling regulates @entity994 expression at transcriptional and/or translational levels. @entity2722 was found to increase the stability of @entity994 message with resultant increase in @entity994 protein level, but it did not alter the protein stability to a great extent. Importantly, knock-down of @entity994 abrogated @entity2722 -induced G(1) arrest suggesting that @entity994 induction by @entity2722 is essential for its G(1) arrest effect. Together, our results for the first time identify a central role of @entity994 induction and associated mechanism in @entity2722 -induced cell cycle arrest in HT29 cells.
