Trisenox induces cytotoxicity through phosphorylation of mitogen‐activated protein kinase molecules in acute leukemia cells

Trisenox (TX) has been used successfully for the treatment of acute promyelocytic leukemia (APL) patients. TX‐induced cytotoxicity in APL cells remains poorly understood. In this study, we investigated the molecular mechanism of TX cytotoxicity using APL cell lines. We assessed TX toxicity by quanti...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2018-10, Vol.32 (10), p.e22207-N/A
Main Authors: Kumar, Sanjay, Farah, Ibrahim O., Tchounwou, Paul B.
Format: Article
Language:English
Subjects:
acute promyelocytic leukemia cell line
Acute promyeloid leukemia
Annexin V
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Arsenic Trioxide - pharmacology
Cell cycle
Cell Cycle - drug effects
Cell Line, Tumor
Confocal microscopy
Cytotoxicity
Drug development
Humans
Immunocytochemistry
Iodides
Kinases
L-Lactate dehydrogenase
L-Lactate Dehydrogenase - metabolism
Lactate dehydrogenase
Lactic acid
Leukemia
Leukemia, Promyelocytic, Acute - enzymology
Leukemia, Promyelocytic, Acute - pathology
MAP kinase
MAP Kinase Signaling System - drug effects
Microscopy
Mitogen-Activated Protein Kinases - metabolism
mitogen‐activated protein kinase signaling
Phosphorylation
Promyeloid leukemia
Propidium iodide
Protein kinase
Proteins
Signaling
Toxicity
Trisenox
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Summary:Trisenox (TX) has been used successfully for the treatment of acute promyelocytic leukemia (APL) patients. TX‐induced cytotoxicity in APL cells remains poorly understood. In this study, we investigated the molecular mechanism of TX cytotoxicity using APL cell lines. We assessed TX toxicity by quantitatively measuring lactate dehydrogenase levels. Inhibition of cell cycle progression was assessed by confocal microscopy of Ki‐67 expression. Apoptosis was evaluated by Western blot analysis of apoptotic proteins expression, immunocytochemistry, and confocal imaging of annexin V and propidium iodide. Mitogen‐activated protein kinase (MAPK) signaling cascade was analyzed by Western blot analysis and inhibitor‐based experiments with APL cells. We found that TX‐induced cytotoxicity inhibited APL cell cycle progression. TX also induced significant (P 
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.22207