HDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation and inhibits telomerase activity.
Bottom Line: Although scriptaid induced activation of both p38MAPK and JNK, it was the inhibition of JNK that attenuated scriptaid-induced apoptosis significantly.Scriptaid also increased the expression of (i) p21 and p27 involved in cell-cycle regulation and (ii) γH2AX associated with DNA damage response in a JNK-dependent manner.Taken together, our findings indicate that scriptaid (i) induces apoptosis and reduces glioma cell proliferation by elevating JNK activation and (ii) also decreases telomerase activity in a JNK-independent manner.
Affiliation: National Brain Research Centre, Manesar, Haryana, India.Show MeSH
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Mentions: HDAC inhibitor-mediated activation of p21WAF1 plays a major role in arresting tumour cell proliferation . As scriptaid significantly inhibited the proliferation of glioma cells, we determined the expression of molecules associated with cell-cycle progression in these cells. Treatment with scriptaid increased the expression of p21 and p27 in a dose-dependent manner (Fig. 3A). The HDAC inhibitor SAHA increases expression of p21 and decreases c-Myc levels in pancreatic cancer cells . As oncoprotein c-Myc suppresses p21WAF1 transcription  and because p21 expression was elevated in scriptaid-treated glioma cells, we determined cMyc expression in these cells. Increase in p21 levels was concomitant with decrease in cMyc expression (Fig. 3A).
Affiliation: National Brain Research Centre, Manesar, Haryana, India.