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HDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation and inhibits telomerase activity.

Sharma V, Koul N, Joseph C, Dixit D, Ghosh S, Sen E - J. Cell. Mol. Med. (2010)

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.

View Article: PubMed Central - PubMed

Affiliation: National Brain Research Centre, Manesar, Haryana, India.

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Scriptaid induces glioma cell-cycle arrest. (A) Scriptaid increases the expression of p21, p27 and decreased cMyc level in glioma cells in a dosedependent manner. LN229 and T98G cells were treated with different concentration of scriptaid for 24 hrs and Western blot analysis was performed to detect the expression of cell-cycle regulatory proteins p21, p27 and cMyc. A representative blot from three independent experiments with identical results is shown. Blots were reprobed for β-actin to establish equivalent loading. (B) Treatment of glioma cells with scriptaid induces G2 arrest in the cell cycle. FACS analysis was performed on cells treated with scriptaid and the percentages of cells in the various cell-cycle phases were plotted. FACS analysis profiles of scriptaidtreated cells are shown. Insets indicate percentage cells in G1, S and G2/M phases of the cell cycle in T98G cells. C and S denote control and scriptaid, respectively.
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fig03: Scriptaid induces glioma cell-cycle arrest. (A) Scriptaid increases the expression of p21, p27 and decreased cMyc level in glioma cells in a dosedependent manner. LN229 and T98G cells were treated with different concentration of scriptaid for 24 hrs and Western blot analysis was performed to detect the expression of cell-cycle regulatory proteins p21, p27 and cMyc. A representative blot from three independent experiments with identical results is shown. Blots were reprobed for β-actin to establish equivalent loading. (B) Treatment of glioma cells with scriptaid induces G2 arrest in the cell cycle. FACS analysis was performed on cells treated with scriptaid and the percentages of cells in the various cell-cycle phases were plotted. FACS analysis profiles of scriptaidtreated cells are shown. Insets indicate percentage cells in G1, S and G2/M phases of the cell cycle in T98G cells. C and S denote control and scriptaid, respectively.

Mentions: HDAC inhibitor-mediated activation of p21WAF1 plays a major role in arresting tumour cell proliferation [22]. 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 [23]. As oncoprotein c-Myc suppresses p21WAF1 transcription [24] 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).


HDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation and inhibits telomerase activity.

Sharma V, Koul N, Joseph C, Dixit D, Ghosh S, Sen E - J. Cell. Mol. Med. (2010)

Scriptaid induces glioma cell-cycle arrest. (A) Scriptaid increases the expression of p21, p27 and decreased cMyc level in glioma cells in a dosedependent manner. LN229 and T98G cells were treated with different concentration of scriptaid for 24 hrs and Western blot analysis was performed to detect the expression of cell-cycle regulatory proteins p21, p27 and cMyc. A representative blot from three independent experiments with identical results is shown. Blots were reprobed for β-actin to establish equivalent loading. (B) Treatment of glioma cells with scriptaid induces G2 arrest in the cell cycle. FACS analysis was performed on cells treated with scriptaid and the percentages of cells in the various cell-cycle phases were plotted. FACS analysis profiles of scriptaidtreated cells are shown. Insets indicate percentage cells in G1, S and G2/M phases of the cell cycle in T98G cells. C and S denote control and scriptaid, respectively.
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Related In: Results  -  Collection

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fig03: Scriptaid induces glioma cell-cycle arrest. (A) Scriptaid increases the expression of p21, p27 and decreased cMyc level in glioma cells in a dosedependent manner. LN229 and T98G cells were treated with different concentration of scriptaid for 24 hrs and Western blot analysis was performed to detect the expression of cell-cycle regulatory proteins p21, p27 and cMyc. A representative blot from three independent experiments with identical results is shown. Blots were reprobed for β-actin to establish equivalent loading. (B) Treatment of glioma cells with scriptaid induces G2 arrest in the cell cycle. FACS analysis was performed on cells treated with scriptaid and the percentages of cells in the various cell-cycle phases were plotted. FACS analysis profiles of scriptaidtreated cells are shown. Insets indicate percentage cells in G1, S and G2/M phases of the cell cycle in T98G cells. C and S denote control and scriptaid, respectively.
Mentions: HDAC inhibitor-mediated activation of p21WAF1 plays a major role in arresting tumour cell proliferation [22]. 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 [23]. As oncoprotein c-Myc suppresses p21WAF1 transcription [24] 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).

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.

View Article: PubMed Central - PubMed

Affiliation: National Brain Research Centre, Manesar, Haryana, India.

Show MeSH
Related in: MedlinePlus