NAD(P)H oxidase isoform Nox2 plays a prosurvival role in human leukaemia cells.
The mechanism involved in the prosurvival effect of interleukin-3 on the human acute myeloid leukaemia cell line M07e is investigated. A decrease in intracellular reactive oxygen species (ROS) content, glucose transport activity and cell survival was observed in the presence of inhibitors of plasma membrane ROS sources, such as diphenylene iodonium and apocynin, and by small interference RNA for Nox2. Moreover, IL-3 incubation stimulated the synthesis of Nox2 cytosolic sub-unit p47phox and glucose transporter Glut1. Thus, the inhibition of ROS generation by Nox inhibitors stimulated apoptosis showing that ROS production, induced by IL-3 via Nox2, protects leukaemic cells from cell death. Also incubation with receptor tyrosine kinase inhibitors, such as anti-leukaemic drugs blocking the stem cell factor receptor (c-kit), showed similar effects, hinting that IL-3 transmodulates c-kit phosphorylation. These mechanisms may play an important role in acute myeloid leukaemia treatment, representing a novel therapeutic target.
Maraldi
Tullia
T
Department of Anatomy and Histology, University of Modena and Reggio Emilia, Modena, Italy.
Prata
Cecilia
C
Vieceli Dalla Sega
Francesco
F
Caliceti
Cristiana
C
Zambonin
Laura
L
Fiorentini
Diana
D
Hakim
Gabriele
G
D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D051272:Glucose Transporter Type 1; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases