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

✍ Scribed by Hiroaki Goto; Masakatsu Yanagimachi; Ryosuke Kajiwara; Fumiko Kuroki; Shumpei Yokota


Publisher
Elsevier Science
Year
2007
Tongue
English
Weight
585 KB
Volume
31
Category
Article
ISSN
0145-2126

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✦ Synopsis


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.