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Updated: Jun 10, 2026
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Abrogating HSP response augments cell death induced by As2O3 in glioma cell lines
Xueming Song1, Zhiqiang Chen, Chunbo Wu
1Department of Neurosurgery, 1st Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, P.R. China.
Objectives:
We previously reported that Arsenic trioxide (ATO) can inhibit glioma growth both in vitro and in vivo. While the use of ATO alone for solid tumor treatment sometimes was found to be ineffective which may be due to the protective pathways including heat shock proteins (HSPs) response induced by ATO. In this study, we modified HSPs expression to investigate whether HSPs had some effect on ATO induced glioma cell death.
Methods:
Trypan bule exclusion assay, mitochondrial membrane potential (MMP) Assay, and SubG1 detection were used to evaluate cell viability and western-blot was employed to detect HSPs and some apoptosis markers expression induced by ATO. Heat pre-treatment, HSPs inhibitor, or Heat Shock factor-1 (HSF1) knockdown by SiRNA was employed to modify HSPs levels.
Results:
It was showed that KNK437 (HSPs inhibitor) or HSF1 knockdown significantly enhanced cell death, MMP disruption, JNK phosphorylation and caspase-3 cleavage induced by ATO, which was accompanied by abrogation of HSPs induction, while heat pre-treatment with clear HSPs induction had strong protection on the effects mentioned above.
Conclusion:
Those data suggested that HSPs play protective roles on ATO induced cell death in glioma. Inhibition of HSPs may have a synergistic effect with ATO on glioma treatment.
Insights
Arsenic trioxide (ATO) shows promise in treating glioma, but heat shock proteins (HSPs) can reduce its effectiveness. Inhibiting HSPs enhances ATO
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Arsenic trioxide (ATO) demonstrated inhibitory effects on glioma growth in prior studies.
- ATO monotherapy for solid tumors can be limited by protective mechanisms, such as heat shock proteins (HSPs) induction.
- Understanding the role of HSPs in ATO-induced glioma cell death is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate the role of heat shock proteins (HSPs) in Arsenic trioxide (ATO)-induced glioma cell death.
- To determine if modulating HSPs expression can enhance the efficacy of ATO in glioma treatment.
Main Methods:
- Cell viability was assessed using trypan blue exclusion, mitochondrial membrane potential (MMP) assays, and SubG1 detection.
- Western blotting was used to analyze the expression of HSPs and apoptosis markers.
- HSPs levels were modulated using heat pre-treatment, an HSPs inhibitor (KNK437), or Heat Shock Factor-1 (HSF1) knockdown via siRNA.
Main Results:
- Inhibition of HSPs (using KNK437 or HSF1 knockdown) significantly increased ATO-induced glioma cell death, MMP disruption, JNK phosphorylation, and caspase-3 cleavage.
- These effects were associated with the abrogation of HSPs induction by ATO.
- Conversely, heat pre-treatment, which strongly induced HSPs, provided significant protection against ATO-induced cell death.
Conclusions:
- Heat shock proteins (HSPs) play a protective role in ATO-induced glioma cell death.
- Inhibiting HSPs may offer a synergistic therapeutic strategy when combined with ATO for glioma treatment.