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: Ras induces DNA damage signalling response  and cells that senesce in response to oncogenic Ras accumulate DNA damage foci . Disruption of cooperation of Ras and cMyc promotes growth arrest of neuroblastoma cells . Moreover, oncogenic Ras promotes HDAC inhibitor butyrate-induced apoptosis . Because scriptaid-triggered apoptosis was concomitant with decrease in cMyc and increase in γ-H2AX, we investigated the contribution of Ras in scriptaid-induced apoptosis. Western blot analysis demonstrated an increase in Ras expression in LN229 and T98G cells upon increasing exposure to scriptaid (Fig. 5A).
Affiliation: National Brain Research Centre, Manesar, Haryana, India.