title: The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines.
abstract: Reactive oxygen species (ROS) are key modulators of apoptosis and carcinogenesis. One of the important sources of ROS is NADPH oxidases (NOXs). The isoform NOX5 is highly expressed in lymphoid tissues, but it has not been detected in any common Hodgkin or non-Hodgkin lymphoma cell lines. In diverse, nonlymphoid malignant cells NOX5 exerts an antiapoptotic effect. Apoptosis suppression is the hallmark feature of a rare type of lymphoma, termed anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and a major factor in the therapy resistance and relapse of ALK(+) ALCL tumors. We applied RT-PCR and Western blot analysis to detect NOX5 expression in three ALK(+) ALCL cell lines (Karpas-299, SR-786, SUP-M2). We investigated the role of NOX5 in apoptosis by small-interfering RNA (siRNA)-mediated gene silencing and chemical inhibition of NOX5 using FACS analysis and examining caspase 3 cleavage in Karpas-299 cells. We used immunohistochemistry to detect NOX5 in ALK(+) ALCL pediatric tumors. NOX5 mRNA was uniquely detected in ALK(+) ALCL cells, whereas cell lines of other lymphoma classes were devoid of NOX5. Transfection of NOX5-specific siRNA and chemical inhibition of NOX5 abrogated calcium-induced superoxide production and increased caspase 3-mediated apoptosis in Karpas-299 cells. Immunohistochemistry revealed focal NOX5 reactivity in pediatric ALK(+) ALCL tumor cells. These results indicate that NOX5-derived ROS contribute to apoptosis blockage in ALK(+) ALCL cell lines and suggest NOX5 as a potential pharmaceutical target to enhance apoptosis and thus to suppress tumor progression and prevent relapse in pediatric ALK(+) ALCL patients that resist classical therapeutic approaches.
authors: Department of Cellular Physiology and Metabolism and; Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland.
authors: S
authors: S
authors: Carnesecchi
authors: Division of Clinical Pathology and.
authors: A-L
authors: AL
authors: Rougemont
authors: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: J H
authors: JH
authors: Doroshow
authors: Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland.
authors: M
authors: M
authors: Nagy
authors: Department of Cellular Physiology and Metabolism and.
authors: S
authors: S
authors: Mouche
authors: Department of Pediatrics, Hematology/Oncology Unit, CANSEARCH Research Laboratory, Geneva, Switzerland.
authors: F
authors: F
authors: Gumy-Pause
authors: Department of Cellular Physiology and Metabolism and; Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland. Electronic address: ildiko.szanto@unige.ch.
authors: I
authors: I
authors: Szanto
mesh_terms: D000293:Adolescent; D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis; D045744:Cell Line, Tumor; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C431571:NOX5 protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic large-cell lymphoma; Apoptosis; Free radicals; Karpas-299; NOX5; Reactive oxygen species