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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
Joint Authors
Mendivil-Perez, Miguel
Velez-Pardo, Carlos
Jimenez-Del-Rio, Marlene
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-23
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
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 O2•->H2O2≫NF-κB (JNK/c-Jun) >p53> loss ΔΨm> 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.
American Psychological Association (APA)
Mendivil-Perez, Miguel& Velez-Pardo, Carlos& Jimenez-Del-Rio, Marlene. 2012. 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. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-14.
https://search.emarefa.net/detail/BIM-462630
Modern Language Association (MLA)
Mendivil-Perez, Miguel…[et al.]. 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. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-14.
https://search.emarefa.net/detail/BIM-462630
American Medical Association (AMA)
Mendivil-Perez, Miguel& Velez-Pardo, Carlos& Jimenez-Del-Rio, Marlene. 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. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-14.
https://search.emarefa.net/detail/BIM-462630
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-462630