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Nitric Oxide and Cancer: Pathogenesis and Therapy pp 203–226Cite as

Emerging Role of NO-Mediated Therapeutics

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Abstract

The free radical nitric oxide (NO) is fundamental in the neoplastic environment. At low concentrations, the gasotransmitter manifests a pathological phenotype characterized by uncontrolled proliferation, increased invasion and metastasis, stimulation of angiogenesis and inhibited apoptosis. Paradoxically, at superphysiological concentrations, a less aggressive phenotype exists, where tumor cells are less likely to metastasize, angiogenesis is inhibited, and apoptotic machinery operates appropriately. This dichotomy of response to NO has created a divergence in the field, with some researchers set on interfering with NO signaling in cancer cells, and others endeavoring to boost it. The purpose of this chapter is to examine the activity of NO in oncology, and to highlight the recent advances in NO-mediated therapeutics. We have focused on emerging strategies that act either by promotion of or interference with NO signaling, including genetic therapies, and have largely limited topics discussed to discoveries from the past 18 months. Attention is paid to agents that have been or are being assessed at clinical trial, and the chapter concludes with a cautionary note on the appropriate use of NO-mediated therapies in oncology.

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Abbreviations

CMV:

Cytomegalovirus

DMBA:

7,12-dimethylbenz[a]anthracene

DT-D:

NAD(P)H:(quinone-acceptor) oxidoreductase

EGF(R):

Epidermal growth factor (receptor)

ELIP:

Echogenic liposomes

ER:

Estrogen receptor

FOLFIRI:

Folinic acid, Fluorouracil, Irinotecan

GST:

Glutathione S-transferase

HNO:

Nitroxyl

HUVEC:

Human umbilical vein endothelial cell

IR:

Ionizing radiation

L-NAME:

L-NG-Nitroarginine methyl ester

MLF2:

Myeloid leukemia factor 2

MMP:

Matrix metalloproteinase

NO(S):

Nitric oxide (synthase)

NONOates:

Diazeniumdiolates

NSAID:

Non-steroidal anti-inflammatory drug

NSCLC:

Non-small cell lung cancer

P-gp:

P-glycoprotein

PARP:

Poly(ADP)ribose polymerase

Pb:

Pheophorbide

PLGA:

Poly(lactic-co-glycolic acid)

PZP:

Polyethylene glycol-conjugated zinc protoporphyrin IX

ROS/RNS:

Reactive oxygen/nitrogen species

RPL39:

Ribosomal protein L39

TIMP:

Tissue inhibitor of metalloproteinase

TPP:

Triphenylphosphonium

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

DEA/NO:

Diethylamine/NO

DETA/NO:

Diethylenetriamine/NO

GLYN:

Glycidyl nitrate

GSNO:

S-nitrosoglutathione

GTN:

Glyceryl trinitrate

INDQ/NO:

Indolequinone-diazeniumdiolate/NO

IPA/NO:

Isopropylamine/NO

JS-K:

(O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1- yl]diazen-1-ium-1,2-diolate)

MNBI:

2-mercapto-5-nitro benzimidazole

NOSH:

Nitric oxide/hydrogen sulfide donor

PABA/NO:

p-aminobenzoic acid/NO

RRx-001:

1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ)

SIN-1:

3-morpholinosydnonimine

SNAP:

S-nitroso- N-acetylpenicillamine

SNO(-HSA):

S-nitrosothiol (-human serum albumin)

SNP:

Sodium nitroprusside

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  1. Experimental Therapeutics Research Group, School of Pharmacy, Queen’s University Belfast, Lisburn Road, BT9 7BL, Belfast, UK

    Cian M. McCrudden & Helen O. McCarthy

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  1. Cian M. McCrudden
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  2. Helen O. McCarthy
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Correspondence to Helen O. McCarthy .

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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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McCrudden, C., McCarthy, H. (2015). Emerging Role of NO-Mediated Therapeutics. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_13

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