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Nitric Oxide and Cancer: Pathogenesis and Therapy pp 247–258Cite as

Regulation of Cell Death Signaling by Nitric Oxide in Cancer Cells

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Abstract

Nitric oxide (NO) is a lipophillic, highly diffusible, and short-lived physiological messenger which regulates a variety of important physiological responses, including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NOS in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways that include post-translational modifications in cysteine (S-nitrosylation), tyrosine nitration and S-nitrosoglutathione-derived compounds. NO sensitizes tumor cells to chemotherapeutic compounds. The antitumoral activity of NO may be related to the regulation of the stress response mediated by the hypoxia inducible factor-1 (HIF-1) and p53 that generally lead to growth arrest, apoptosis or adaptation. In addition, the post-translational regulation of cell death receptors modulates the apoptotic pathways.

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Abbreviations

BH4:

(6R)-5,6,7,8-tetrahydrobiopterin

bZip:

Basic Leucine Zipper

CaM:

Calmodulin

DR:

Death Receptor

ECM:

Extracellular Matrix

eNOS (NOS-3):

Endothelial NOS

GTN:

Glyceryl Trinitrate

GSH:

Reduced Glutathione

GSNO:

S-nitrosoglutathione

haeme:

Iron Protoporphyrin IX

HIF-1:

Hypoxia Inducible Factor-1

iNOS:

Inducible NOS

MAPK:

Mitogen-Activated Protein Kinases

nNOS (NOS-1):

Neuronal NOS

NO:

Nitric Oxide

NOS:

Nitric Oxide Synthases

O2•− :

Anion Superoxide

PI3K:

Phosphatidylinositol-3 kinase

PSA:

Prostate-Specific Antigen

sGC:

Soluble Guanylate Cyclase

TRAIL:

Tumor Necrosis Factor-Related Apoptosis Inducing Ligand

TRAIL-R1:

TRAIL Receptor 1

TRAIL-R2:

TRAIL Receptor 2

TNF-R1:

Tumor Necrosis Factor Receptor Type 1

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Acknowledgements

We thank the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by “Carlos III” Health Institute for its support.

Conflict Statement

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of General Surgery, Hospital Universitario Virgen del Rocío-Virgen Macarena/IBiS/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Sevilla, Spain

    Dr. Jordi Muntané, Luís M. Marín, Jose M. Álamo & Francisco J. Padillo

  2. Instituto de Biomedicina de Sevilla (IBiS), IBiS/Hospital Universitario Virgen del Rocío-Virgen Macarena/Universidad de Sevilla/CSIC, Av. Manuel Siurot s/n, 41013, Seville, Spain

    Dr. Jordi Muntané, Francisco Gallardo-Chamizo, Sheila Pereira, Ángela M. De los Santos & Ángeles Rodríguez-Hernández

  3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREH o Ciberehd), Instituto de Salud Carlos III, Madrid, Spain

    Dr. Jordi Muntané, Luís M. Marín, Jose M. Álamo & Francisco J. Padillo

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  1. Dr. Jordi Muntané
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  1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California of Los Angeles, Los Angeles, California, USA

    Benjamin Bonavida

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Muntané, J. et al. (2015). Regulation of Cell Death Signaling by Nitric Oxide in Cancer Cells. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_15

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