Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several epidemiological studies have demonstrated that vitamin E is a chemopreventative agent for prostate cancer. alpha-Tocopheryl succinate (VES), a derivative of vitamin E, effectively modulates prostate cancer cell growth. However, little is known about the mechanisms regarding this action. Here we show that VES causes human prostate cancer cell LNCaP arrest at G1 phase. This effect is accomplished through VES significantly decreasing expression of the cell cycle regulatory proteins cyclin D1, D3, and E, cdk2 and 4, but not cdk6. Furthermore, VES reduces cdk4 kinase activity, Rb phosphorylation, and cyclin E mRNA expression. Recently there is increasing interest in the protective effect of the VES and selenium combination on prostate cancer. Here we show that VES and selenium work through different mechanisms to exert their inhibitory effects on prostate cancer cells. Taken together, our studies suggest that VES-mediated prostate cancer cell G1/S arrest is a consequence of the regulation of multiple molecules of the cell cycle regulatory machinery.
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PMID:Vitamin E succinate inhibits human prostate cancer cell growth via modulating cell cycle regulatory machinery. 1250 91

The biochemical pathways involved in neuronal cell death in Parkinson's disease are not completely characterized. Mitochondrial dysfunction, specifically alteration of the mitochondrial complex I, is the primary target of the parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) induced apoptosis in neurons. In the present study, we examine the role of caspase-dependent and -independent routes in MPP+-induced apoptosis in rat cerebellar granule neurons (CGNs). We show a distinct increase in the expression of the cell cycle proteins cyclin D, cyclin E, cdk2, cdk4 and the transcription factor E2F-1 following a MPP+ treatment of CGNs. Flavopiridol (FLAV), a broad inhibitor of cyclin-dependent kinases (CDKs), attenuated the neurotoxic effects of MPP+ and significantly attenuates apoptosis mediated by MPP+ 200 microM. Likewise, the antioxidant vitamin E (vit E) increases neuronal cell viability and attenuates apoptosis induced by MPP+. Moreover, the expression levels of cyclin D and E2F-1 induced by this parkinsonian neurotoxin were also attenuated by vit E. Since, the broad-spectrum caspase inhibitor zVAD-fmk did not attenuate MPP+-induced apoptosis in CGNs, our data provide a caspase-independent mechanism mediated by neuronal reentry in the cell cycle and increased expression of the pro-apoptotic transcription factor E2F-1. Our results also suggest a potential role of oxidative stress in neuronal reentry in the cell cycle mediated by MPP+. Finally, our data further support the therapeutic potential of flavopiridol, for the treatment of Parkinson's disease.
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PMID:Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons. 1734 87