Lack of mitochondrial depolarization by oxidative stress is associated with resistance to buthionine sulfoximine in acute lymphoblastic leukemia cells

Abstract Raised intracellular glutathione is one characteristics of high-risk childhood acute lymphoblastic leukemia (ALL). Depletion of glutathione by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells. To assess the role of glutathione in ALL, the toxicity of BSO...

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Bibliographic Details
Published in:Leukemia research 2007-09, Vol.31 (9), p.1293-1301
Main Authors: Goto, Hiroaki, Yanagimachi, Masakatsu, Kajiwara, Ryosuke, Kuroki, Fumiko, Yokota, Shumpei
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Anti-Inflammatory Agents - pharmacology
Antimetabolites, Antineoplastic - therapeutic use
Buthionie sulfoximine
Buthionine Sulfoximine - therapeutic use
Cell Proliferation - drug effects
Drug Resistance, Neoplasm
Glutathione
Glutathione - metabolism
Hematology, Oncology and Palliative Medicine
Humans
Hydrogen Peroxide - pharmacology
Membrane Potentials - drug effects
Mitochondria
Mitochondria - metabolism
Oxidants - pharmacology
Oxidative Stress
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Prednisolone - pharmacology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Tumor Cells, Cultured - drug effects
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Summary:Abstract Raised intracellular glutathione is one characteristics of high-risk childhood acute lymphoblastic leukemia (ALL). Depletion of glutathione by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells. To assess the role of glutathione in ALL, the toxicity of BSO was studied in B-precursor ALL cell lines. BSO increased oxidative stress equally in all cell lines; however mitochondrial depolarization was observed only in BSO-sensitive cells. BSO up-regulated Bcl-2 protein, and antagonized the anti-ALL effect of prednisolone in BSO-resistant cells. A lack of mitochondrial death-signal activation by oxidative stress seemed to be associated with BSO-resistance in ALL.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2007.01.003