Lack of mitochondrial depolarization by oxidative stress is associated with resistance to buthionine sulfoximine in acute lymphoblastic leukemia cells.
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.
Goto
Hiroaki
H
Department of Pediatrics, Yokohama City University Hospital, 3-9 Fukuura Kanazawa-ku, Yokohama 236-0044, Japan. hgoto39@med.yokohama-cu.ac.jp
Yanagimachi
Masakatsu
M
Kajiwara
Ryosuke
R
Kuroki
Fumiko
F
Yokota
Shumpei
S
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D019328:Buthionine Sulfoximine / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000964:Antimetabolites, Antineoplastic; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D019328:Buthionine Sulfoximine; D011239:Prednisolone; D006861:Hydrogen Peroxide; D005978:Glutathione