title: Neuroglobin in Breast Cancer Cells: Effect of Hypoxia and Oxidative Stress on Protein Level, Localization, and Anti-Apoptotic Function.
abstract: The over-expression of human neuroglobin (NGB), a heme-protein preferentially expressed in the brain, displays anti-apoptotic effects against hypoxic/ischemic and oxidative stresses enhancing neuron survival. As hypoxic and oxidative stress injury frequently occurs in fast proliferating neoplastic tissues, here, the effect of these stressors on the level, localization, and anti-apoptotic function of NGB in wild type and NGB-stable-silenced MCF-7 breast cancer cells has been assessed. The well-known endogenous NGB inducer 17β-estradiol (E2) has been used as positive control. The median pO2 present in tumor microenvironment of breast cancer patients (i.e., 2% O2) does not affect the NGB level in breast cancer cells, whereas hydrogen peroxide and lead(IV) acetate, which increase intracellular reactive oxygen species (ROS) level, enhance the NGB levels outside the mitochondria and still activate apoptosis. However, E2-induced NGB up-regulation in mitochondria completely reverse lead(IV) acetate-induced PARP cleavage. These results indicate that the NGB level could represent a marker of oxidative-stress in MCF-7 breast cancer cells; however, the NGB ability to respond to injuring stimuli by preventing apoptosis requires its re-allocation into the mitochondria. As a whole, present data might lead to a new direction in understanding NGB function in cancer opening new avenues for the therapeutic intervention.
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiocchetti
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cipolletti
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Naldini
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Carraro
authors.affiliation: Biosciences and BioResources Institute-CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giordano
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.|Biosciences and BioResources Institute-CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Verde
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.|Biosciences and BioResources Institute-CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.|Interdepartmental Laboratory of Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, I-00146 Roma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.affiliation: Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.|Biosciences and BioResources Institute-CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005914:Globins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D017382:Reactive Oxygen Species; D005914:Globins; D006861:Hydrogen Peroxide