ArticleJournal of hematology & oncology2010
Basic mechanisms of arsenic trioxide (ATO)-induced apoptosis in human leukemia (HL-60) cells.
Article in Journal of hematology & oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 102 citations in OpenAlex.
- A phase II trial of arsenic trioxide and temozolomide in combination with radiation therapy for patients with malignant gliomas.Journal of neuro-oncology · 2017Trial
- Exploring Interactive Effects of Arsenic and Selenium Exposure on Larval Zebrafish (Danio rerio).Environmental toxicology · 2026Article
- Bacillus thuringiensis Sublethal Concentration Effectively Alter Cytogenetic Response of Spodoptera frugiperda Larvae.Neotropical entomology · 2026Article
- Synergistic effects of arsenic trioxide and atorvastatin on proliferation and apoptosis in acute lymphoblastic leukemia cells.Leukemia research reports · 2026Article
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- The outcast of medicine: metals in medicine--from traditional mineral medicine to metallodrugs.Frontiers in pharmacology · 2025Review
- The role of mitochondrial dysfunction in the cytotoxic synergistic effect of gemcitabine and arsenic on breast cancer.PloS one · 2025Article
- Review
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Combination Effect of Deferoxamine and Arsenic Trioxide on Viability and Vitality of APL Like Cell Line.Ethiopian journal of health sciences · 2023Article
- CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia.Asian journal of pharmaceutical sciences · 2023Article
- Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer.Biological trace element research · 2023Article
- Review
- Article
- Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects.Nature nanotechnology · 2021Article
- Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells.Environmental toxicology · 2021Article
- Arsenic-induced uterine apoptotic damage is protected by ethyl acetate fraction of Camellia sinensis (green tea) via Bcl-2-BAX through NF-κB regulations in Wistar rats.Environmental science and pollution research international · 2021Article
- The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun.BMC cancer · 2020Article
- Trisenox Disrupts MDM2-DAXX-HAUSP Complex and Induces Apoptosis in a Mouse Model of Acute Leukemia.Journal of Cancer · 2020Article
- Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAcute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leukemia cells.
methodsIn the present study, we further investigated the apoptotic mechanisms of ATO toxicity using the HL-60 cell line as a test model. Apoptosis was measured by flow cytometry analysis of phosphatidylserine externalization (Annexin V assay) and caspase 3 activity, and by DNA laddering assay.
resultsFlow cytometry data showed a strong dose-response relationship between ATO exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p <0.05) was recorded with regard to caspase 3 activity in HL60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in ATO-treated cells.
conclusionTaken together, our research demonstrated that ATO represents an apoptosis-inducing agent and its apoptotic mechanisms involve phosphatidylserine externalization, caspase 3 activation and nucleosomal DNA fragmentation.
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