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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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Related in: MedlinePlus

Scriptaid-mediated DNA damage response and alteration in cellcycle regulatory molecules in glioma cells are JNK dependent. Glioma cells were treated with 20 μM scriptaid in the presence or absence of 20 μM JNK inhibitor SP600125, and Western blot analysis was performed. A decrease in pJNK, p21, p27 and H2AX expression respectively was observed in cells treated with scriptaid in the presence of JNK inhibitor, as compared to those treated with Scripatid alone. Representative blot is shown from three independent experiments with identical results. Blots were reprobed for β-actin to establish equivalent loading.
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fig07: Scriptaid-mediated DNA damage response and alteration in cellcycle regulatory molecules in glioma cells are JNK dependent. Glioma cells were treated with 20 μM scriptaid in the presence or absence of 20 μM JNK inhibitor SP600125, and Western blot analysis was performed. A decrease in pJNK, p21, p27 and H2AX expression respectively was observed in cells treated with scriptaid in the presence of JNK inhibitor, as compared to those treated with Scripatid alone. Representative blot is shown from three independent experiments with identical results. Blots were reprobed for β-actin to establish equivalent loading.

Mentions: Inhibition of tumour cell-cycle arrest through JNK activation has been reported [34]. Because JNK activation is involved in scriptaid-induced glioma cell death, we investigated whether JNK pathway modulate cell-cycle regulatory proteins by determining p21 and p27 expression in glioma cells treated with scriptaid in the presence and absence of JNK inhibitors. The increased p21 and p27 expression observed upon scriptaid treatment was reversed in the presence of JNK inhibitor (Fig. 6). Ras induces DNA damage signalling response [28] and JNK activation radiosensitizes colon carcinoma cells through enhanced DNA damage [35]. Because increased Ras and JNK activation was observed in scriptaid-treated cells, we determined the expression of γ-H2AX in cells treated with scriptaid in the presence and absence of JNK inhibitors. The elevated levels of γH2AX observed in scriptaid-treated cells were abrogated to control levels in the presence of JNK inhibitor (Fig. 7). The increase in pJNK levels observed in scriptaid-treated cells was decreased to control levels in the presence of JNK inhibitor. These results indicate the involvement of JNK in scriptaid-induced DSB response in glioma cells.


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-mediated DNA damage response and alteration in cellcycle regulatory molecules in glioma cells are JNK dependent. Glioma cells were treated with 20 μM scriptaid in the presence or absence of 20 μM JNK inhibitor SP600125, and Western blot analysis was performed. A decrease in pJNK, p21, p27 and H2AX expression respectively was observed in cells treated with scriptaid in the presence of JNK inhibitor, as compared to those treated with Scripatid alone. Representative blot is shown from three independent experiments with identical results. Blots were reprobed for β-actin to establish equivalent loading.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3823006&req=5

fig07: Scriptaid-mediated DNA damage response and alteration in cellcycle regulatory molecules in glioma cells are JNK dependent. Glioma cells were treated with 20 μM scriptaid in the presence or absence of 20 μM JNK inhibitor SP600125, and Western blot analysis was performed. A decrease in pJNK, p21, p27 and H2AX expression respectively was observed in cells treated with scriptaid in the presence of JNK inhibitor, as compared to those treated with Scripatid alone. Representative blot is shown from three independent experiments with identical results. Blots were reprobed for β-actin to establish equivalent loading.
Mentions: Inhibition of tumour cell-cycle arrest through JNK activation has been reported [34]. Because JNK activation is involved in scriptaid-induced glioma cell death, we investigated whether JNK pathway modulate cell-cycle regulatory proteins by determining p21 and p27 expression in glioma cells treated with scriptaid in the presence and absence of JNK inhibitors. The increased p21 and p27 expression observed upon scriptaid treatment was reversed in the presence of JNK inhibitor (Fig. 6). Ras induces DNA damage signalling response [28] and JNK activation radiosensitizes colon carcinoma cells through enhanced DNA damage [35]. Because increased Ras and JNK activation was observed in scriptaid-treated cells, we determined the expression of γ-H2AX in cells treated with scriptaid in the presence and absence of JNK inhibitors. The elevated levels of γH2AX observed in scriptaid-treated cells were abrogated to control levels in the presence of JNK inhibitor (Fig. 7). The increase in pJNK levels observed in scriptaid-treated cells was decreased to control levels in the presence of JNK inhibitor. These results indicate the involvement of JNK in scriptaid-induced DSB response in glioma cells.

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