Arsenic trioxide inhibits glioma cell growth through induction of telomerase displacement and telomere dysfunction
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Updated: Mar 25, 2026
Evaluating In Vitro DNA Damage Using Comet Assay
Published on: October 11, 2017
Ye Cheng1, Yunqian Li1, Chengyuan Ma1
1Department of Neurosurgery, First Hospital of Jilin University, Changchun, P. R. China.
Abstract:
Glioblastomas are resistant to many kinds of treatment, including chemotherapy, radiation and other adjuvant therapies. As2O3 reportedly induces ROS generation in cells, suggesting it may be able to induce telomerase suppression and telomere dysfunction in glioblastoma cells. We show here that As2O3 induces ROS generation as well as telomerase phosphorylation in U87, U251, SHG4 and C6 glioma cells. It also induces translocation of telomerase from the nucleus to the cytoplasm, thereby decreasing total telomerase activity. These effects of As2O3 trigger an extensive DNA damage response at the telomere, which includes up-regulation of ATM, ATR, 53BP1, γ-H2AX and Mer11, in parallel with telomere fusion and 3'-overhang degradation. This ultimately results in induction of p53- and p21-mediated cell apoptosis, G2/M cell cycle arrest and cellular senescence. These results provide new insight into the antitumor effects of As2O3 and can perhaps contribute to solving the problem of glioblastoma treatment resistance.
Insights
Arsenic trioxide (As2O3) combats glioblastoma by inducing oxidative stress, telomere damage, and DNA damage, leading to cancer cell death and senescence. This offers a potential new strategy against treatment-resistant brain tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastomas exhibit significant resistance to conventional therapies like chemotherapy and radiation.
- Arsenic trioxide (As2O3) is known to induce reactive oxygen species (ROS) generation in cells.
- This ROS generation suggests a potential mechanism for As2O3 in targeting telomerase and telomere integrity in glioblastoma.
Purpose of the Study:
- To investigate the effects of As2O3 on telomerase activity and telomere function in glioblastoma cells.
- To elucidate the molecular mechanisms underlying As2O3-induced glioblastoma cell death and growth arrest.
Main Methods:
- Treatment of U87, U251, SHG4, and C6 glioma cells with As2O3.
- Measurement of ROS generation and telomerase phosphorylation.
- Analysis of telomerase localization and activity.
- Assessment of DNA damage response markers (ATM, ATR, 53BP1, γ-H2AX, Mer11), telomere fusion, and 3'-overhang degradation.
- Evaluation of apoptosis, cell cycle arrest, and senescence induction.
Main Results:
- As2O3 induced ROS generation and telomerase phosphorylation in all tested glioma cell lines.
- As2O3 caused telomerase translocation from the nucleus to the cytoplasm, reducing overall telomerase activity.
- Significant DNA damage response at telomeres was observed, including upregulation of key damage markers.
- Telomere fusion and 3'-overhang degradation were induced by As2O3 treatment.
- As2O3 triggered p53- and p21-mediated apoptosis, G2/M cell cycle arrest, and cellular senescence.
Conclusions:
- As2O3 effectively induces telomere dysfunction and DNA damage in glioblastoma cells via ROS generation.
- The observed effects lead to apoptosis, cell cycle arrest, and senescence, highlighting As2O3's potent antitumor activity.
- These findings offer a novel therapeutic approach for overcoming glioblastoma treatment resistance.
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