ArticleOxidative medicine and cellular longevity2012
TPEN induces apoptosis independently of zinc chelator activity in a model of acute lymphoblastic leukemia and ex vivo acute leukemia cells through oxidative stress and mitochondria caspase-3- and AIF-dependent pathways.
Article in Oxidative medicine and cellular longevity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 69 citations in OpenAlex.
- TPEN, a Well-Known Zinc Chelator, Sequesters Attomolar-Buffered Cellular Cu(I) Through an Oxygen-Dependent Mechanism.ACS chemical neuroscience · 2026Article
- A combination of artemisinin, moxidectin, and doxorubicin drugs can selectively and efficiently induce apoptosis in acute lymphoblastic and chronic myeloid leukemia cells in vitro and ex vivo.Medical oncology (Northwood, London, England) · 2026Article
- Presenilin 1 E280A mutation induces dysfunctional astrocytic phenotype in menstrual stromal-derived astrocyte-like cells.Cellular and molecular life sciences : CMLS · 2025Article
- PPARγ regulates osteoarthritis chondrocytes apoptosis through caspase-3 dependent mitochondrial pathway.Scientific reports · 2024Article
- ZneLife · 2023Article
- ZnbioRxiv : the preprint server for biology · 2023Article
- The Role of Swelling in the Regulation of OPA1-Mediated Mitochondrial Function in the Heart In Vitro.Cells · 2023Article
- Article
- TPEN selectively eliminates lymphoblastic B cells from bone marrow pediatric acute lymphoblastic leukemia patients.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells.International journal of molecular sciences · 2022Article
- Combinational treatment of TPEN and TPGS induces apoptosis in acute lymphoblastic and chronic myeloid leukemia cells in vitro and ex vivo.Medical oncology (Northwood, London, England) · 2022Article
- Adherence Enables Neisseria gonorrhoeae to Overcome Zinc Limitation Imposed by Nutritional Immunity Proteins.Infection and immunity · 2022Article
- Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses.Antioxidants (Basel, Switzerland) · 2021Review
- TPEN exerts selective anti-leukemic efficacy in ex vivo drug-resistant childhood acute leukemia.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Zinc Modulates Several Transcription-Factor Regulated Pathways in Mouse Skeletal Muscle Cells.Molecules (Basel, Switzerland) · 2020Article
- Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle.eLife · 2020Article
- Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia.Cancers · 2019Article
- The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- Synthetic Cyclic Peptomers as Type III Secretion System Inhibitors.Antimicrobial agents and chemotherapy · 2017Article
- Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma.Oncology letters · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lymphoblastic leukemia is still an incurable disease with resistance to therapy developing in the majority of patients. We investigated the effect of TPEN, an intracellular zinc chelator, in Jurkat and in ex vivo acute lymphoblastic leukemia (ALL) cells resistant to chemotherapy. Changes of nuclei morphology, reactive oxygen species generation, presence of hypodiploid cells, phosphatidylserine translocation, mitochondrial membrane depolarization, immunohistochemical identification of cell death signalling molecules, and pharmacological inhibition were assayed to detect the apoptotic cell death pathways. We found that TPEN induces apoptosis in both types of cells by a molecular oxidative stress pathway involving O(2)(•-) > H(2)O(2) >> NF-κB (JNK/c-Jun) >p53> loss ΔΨ(m)> caspase-3, AIF > chromatin condensation/DNA fragmentation. Interestingly, TPEN induced apoptosis independently of glucose; leukemic cells are therefore devoid of survival capacity by metabolic resistance to treatment. Most importantly, TPEN cytotoxic effect can eventually be regulated by the antioxidant N-acetyl-cysteine and zinc ions. Our data suggest that TPEN can be used as a potential therapeutic prooxidant agent against refractory leukemia. These data contribute to understanding the importance of oxidative stress in the treatment of ALL.
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