Abstract
The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. The present study aimed to investigate the enhanced effects and mechanisms in apoptosis and the cycle distribution of HL-60 cells, a human leukemia cell line lacking a functional p53 protein, after combination treatment with arsenic trioxide (ATO) and irradiation (IR). Our results indicated that combined treatment led to increased cytotoxicity and apoptotic cell death in HL-60 cells, which was correlated with the activation of cdc-2 and increased expression of cyclin B, the induction of intracellular reactive oxygen species (ROS) generation, the loss of mitochondria membrane potential, and the activation of caspase-3. The combined treatment of HL-60 cells pre-treated with Z-VAD or NAC resulted in a significant reduction in apoptotic cells. In addition, activation of JNK and p38 MAPK may be involved in combined treatment-mediated apoptosis. The data suggest that a combination of IR and ATO could be a potential therapeutic strategy against p53-deficient leukemia cells.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / pharmacology
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects*
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Apoptosis / radiation effects*
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Arsenic Trioxide
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Arsenicals / pharmacology*
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Caspase 3 / metabolism
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Cell Cycle / drug effects
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Cell Cycle / radiation effects
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Cell Cycle Proteins / metabolism
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Cyclins / metabolism
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DNA Fragmentation / drug effects
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DNA Fragmentation / radiation effects
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Dose-Response Relationship, Drug
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Dose-Response Relationship, Radiation
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F-Box Proteins / metabolism
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F-Box-WD Repeat-Containing Protein 7
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HL-60 Cells
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Humans
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / radiation effects
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Models, Biological
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Oxides / pharmacology*
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Phosphorylation / drug effects
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Phosphorylation / radiation effects
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Reactive Oxygen Species / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Signal Transduction / radiation effects
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Tumor Stem Cell Assay
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Ubiquitin-Protein Ligases / metabolism
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X-Rays
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bcl-2-Associated X Protein / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Antineoplastic Agents
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Arsenicals
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BAX protein, human
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Cell Cycle Proteins
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Cyclins
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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Oxides
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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bcl-2-Associated X Protein
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Ubiquitin-Protein Ligases
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Poly(ADP-ribose) Polymerases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Caspase 3
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Arsenic Trioxide
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Acetylcysteine