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Updated: Jun 3, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 in trichostatin A induced C6 glioma cell death
Ya-Fen Hsu1, Joen-Rong Sheu, George Hsiao
1Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Background:
Histone deacetylase (HDAC) inhibitors were demonstrated to induce cell cycle arrest, promote cell differentiation or apoptosis, and inhibit metastasis. HDAC inhibitors have thus emerged as a new class of anti-tumor agents for various types of tumors. However, the mechanisms by which HDAC inhibition-induced cell death remain to be fully defined.
Methods:
In the present study, we explored the apoptotic actions of trichostatin A (TSA), a HDAC inhibitor, in C6 glioma cells.
Results:
TSA activated p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation and activation. P53, a proapoptotic transcription factor, in turn transactivated the expression of a proapoptotic protein, Bax. In addition, survivin, a member of inhibitor of apoptotic protein, was significantly decreased in TSA-treated C6 cells. P53 recruited to the endogenous survivin promoter region was increased and accompanied by decreasing recruitment of SP1 in response to TSA. TSA was also shown to induce IKK dephosphorylation and to suppress NF-κB reporter activity.
Conclusions:
TSA may cause C6 cell apoptosis through activating p38MAPK-p53 cascade resulting in Bax expression and survivin suppression. Negative regulation of IKK-NF-κB signaling may also lead to p53 activation and contribute to TSA apoptotic actions.
General Significance:
TSA-induced p53 activation may occur through p53 modification by phosphorylation or by acetylation via IKK inactivation. The present study delineates, in part, the signaling pathways involved in TSA-induced glioma cell death.
Insights
Histone deacetylase (HDAC) inhibitors like trichostatin A (TSA) induce glioma cell death. TSA activates the p38MAPK-p53 pathway, increasing apoptosis and decreasing survival proteins.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Histone deacetylase (HDAC) inhibitors are a promising anti-tumor drug class.
- HDAC inhibitors induce cell cycle arrest, differentiation, apoptosis, and inhibit metastasis.
- Mechanisms of HDAC inhibitor-induced cell death require further elucidation.
Purpose of the Study:
- To investigate the apoptotic effects of trichostatin A (TSA) in C6 glioma cells.
- To define the molecular pathways involved in TSA-induced glioma cell death.
Main Methods:
- Treatment of C6 glioma cells with trichostatin A (TSA).
- Analysis of p38 mitogen-activated protein kinase (p38MAPK) activation.
- Assessment of p53 phosphorylation, transactivation, and promoter recruitment.
- Measurement of survivin and SP1 protein levels and promoter binding.
- Evaluation of IκB kinase (IKK) dephosphorylation and NF-κB reporter activity.
Main Results:
- TSA activated the p38MAPK pathway, leading to p53 phosphorylation and activation.
- Activated p53 transactivated Bax expression and suppressed survivin expression.
- TSA treatment decreased survivin levels and increased p53 binding to the survivin promoter while decreasing SP1 binding.
- TSA induced IKK dephosphorylation and suppressed NF-κB reporter activity.
Conclusions:
- TSA induces C6 glioma cell apoptosis via the p38MAPK-p53 cascade, upregulating Bax and downregulating survivin.
- Inhibition of IKK-NF-κB signaling contributes to p53 activation and TSA's apoptotic effects.
- TSA-induced p53 activation may involve phosphorylation or acetylation, potentially mediated by IKK inactivation.
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