ArticleInternational journal of molecular sciences2023
ATO Increases ROS Production and Apoptosis of Cells by Enhancing Calpain-Mediated Degradation of the Cancer Survival Protein TG2.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Rethinking Drug Resistance in Acute Promyelocytic Leukemia: The Regulated Cell Death Network as an Integrative Framework.Biomolecules · 2026Review
- Astragalus polysaccharides inhibit arsenic trioxide-induced BMSCs damage through inhibition of Jnk and p38 signaling pathways.Chinese herbal medicines · 2026Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Synergistic Enhancement of Apo2L/TRAIL and DR4-Induced Apoptosis by Arsenic Trioxide in Triple-Negative Breast Cancer Cells: A Comparison to Conventional Chemotherapy.Cell biochemistry and biophysics · 2025Article
- Comparative effects of arsenic trioxide and chemotherapy on Chk1 and CDC25 gene expression in gastric cancer cells AGS and MKN45: a potential therapeutic strategy.Molecular biology reports · 2025Article
- Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.Current pharmacology reports · 2024Article
- RSL3 sensitizes glioma cells to ionizing radiation by suppressing TGM2-dependent DNA damage repair and epithelial-mesenchymal transition.Redox biology · 2024Article
- Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date.Archives of pharmacal research · 2024Review
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signalling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial-mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukaemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukaemia cells, and that these responses were enhanced when TG2 was deleted. The combined ATRA + ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of the cellular oxidative stress response, and calpain proteolytic activity, resulting in TG2 degradation and the reduced survival of WT leukaemia cells. We further showed that the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line and primary peripheral blood mononuclear cells upon ATO treatment, thereby sensitising these cell types to apoptotic signals.
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