title: Fenretinide cytotoxicity is independent of both constitutive and pharmacologically modulated glutathione levels in pediatric acute lymphoblastic leukemia cells cultured at hypoxia.
abstract: Fenretinide (4-HPR) cytotoxicity relative to glutathione levels in pediatric acute lymphoblastic leukemia cell lines cultured at bone marrow level hypoxia (5% O2) is evaluated. 4-HPR cytotoxicity correlated with reactive oxygen species generation (P < 0.001),but not with levels of intracellular glutathione, g-glutamylcysteine synthase, or glutathione peroxidase. Buthionine sulfoximine (BSO)reduced glutathione levels in 10 cell lines (P < 0.001), but 4-HPR þ BSO was markedly synergistic in only 1 of 10 lines. Pretreatment with N-acetylcysteine increased glutathione (P < 0.02)but did not alter 4-HPR cytotoxicity. Our data suggest that 4-HPR cytotoxicity is independent of glutathione under physiologic oxygen tension.
authors.affiliation: School of Medicine, Texas Tech University HealthSciences Center, Lubbock, TX, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Cooper
authors.forename: Sookhee
authors.initials: S
authors.lastname: Bang
authors.forename: Hardeep
authors.initials: H
authors.lastname: Singh
authors.forename: Simon C
authors.initials: SC
authors.lastname: Williams
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D017313:Fenretinide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D017313:Fenretinide; D005978:Glutathione