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Assessing the Contributions of Lipid Profile and Oxidative Lipid Damage to Carcinogenesis

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

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Abstract

Lipids are integral components in the body, performing various structural and functional roles – as energy reservoirs, insulators, cell membrane components, hormone precursors, and as key signalling agents which affect cellular metabolism and gene expression. Dysregulation of redox proteins/enzymes involved in the process of redox homeostasis and generation of nonphysiological levels of free radicals causes oxidative stress, an important nexus in the pathogenesis and pathophysiology of several diseases, including cancer. Oxidative damage to lipids causes lipid peroxidation, a process which leads to the formation of toxic aldehydes and other secondary products, which sometimes have beneficial roles at physiological levels. However, oxidative stress-mediated lipid peroxidation products initiate carcinogenesis through macromolecular damage (DNA/RNA/protein adduction), inhibition of DNA repair, and alteration of the cellular transcriptome. The problem of lipid damage poses a conundrum, where lipid damage/oxidation products can be both beneficial as well as harmful in a dose-dependent manner. This chapter is aimed at deciphering the mechanisms of lipid oxidation and the cellular signalling events mediated by lipid damage products which determine important cellular outcomes. The toxic products cause a plethora of effects such as impairment of mitochondrial energy metabolism, membrane protein dysfunction, alteration of the cellular transcriptome, upregulation of antioxidant gene transcription, depletion of the cellular thiol pool, genomic instability, ferroptosis, etc., and thereby, pathogenesis of several cancers. The roles of dietary lipids, blood lipid profile, cellular distribution of diverse endogenous and/or dietary lipids, and finally, the currently known mechanisms of oxidative lipid damage in carcinogenesis/tumorigenesis are reviewed.

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Abbreviations

4HNE/HNE:

4-hydroxynonenal

AA:

Arachidonic acid

ALA:

Alpha-linolenic acid

ALOX:

Lipoxygenase

ARE:

Antioxidant response element

CAT:

Catalase

CLs:

Cardiolipins

COQ10/UQ:

CoenzymeQ10/ubiquinone

COX-2:

Cyclooxygenase

CROALD:

Crotonaldehyde

CYP450/CYPs:

Cytochrome P450

DHA:

Docosahexaenoic acid

DODE:

9,12-dioxo-(10E)-dodecenoic acid

DOOE:

5,8-dioxo10(E)-octenoic acid

EBV:

Epstein–Barr virus

ECM:

Extracellular matrix

EDE:

4,5-epoxy-(2E)-decenal

EDGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EHN/EH:

2,3-epoxy-4-hydroxynonanal

EPA:

Eicosapentaenoic acid

ERK:

Extracellular signal-regulated kinase

ESRE:

Ethanol and stress response element

ETC:

Electron transfer chain

FA/FAs:

Fatty acids

FRs:

Free radicals

GA:

Gondoic acid

GCL:

γ-glutamylcysteine ligase/glutamate-cysteine ligase

GLA:

Gamma-linolenic acid

GPx:

Glutathione peroxidase

GSK3β:

Glycogen synthase kinase-3 beta

GST:

Glutathione S-transferases

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HDHA:

Hydroxy-docosahexaenoic acid

HEPE:

Hydroxyeicosapentaenoic acid

HETE:

Hydroxyeicosatetraenoic acid

HHE:

4-hydroxy-2-hexenal

HHV:

Human herpes virus

HO:

Heme oxygenase

HODE:

Hydroxyoctadecadienoic acid

HPHE:

4-hydroperoxy-2-heptenal

HPNE:

4-hydroperoxy-2-nonenal

HSE:

Heat-stress-responsive element

HTLV:

Human T-lymphotropic virus

HUE:

4-hydroxyundecenal

HX:

Hepoxilins

iNOS:

Inducible nitric oxide synthase

Keap1 :

Kelch-like ECH-associated protein 1

LA:

Linoleic acid

LOOHs:

Lipid hydroperoxides

LOX:

Lipoxygenase

LPO:

Lipid peroxidation

LT:

Leukotrienes

MAPK:

Mitogen-activated protein kinase

MaR:

Maresins

MDA:

Malondialdehyde

MPO:

Myeloperoxidase

MUFA:

Monounsaturated fatty acids

NA:

Nervonic acid

NFκB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NOS:

Nitric oxide synthases

NOX:

NADPH oxidase

Nrf-2:

Nuclear factor erythroid 2–related factor 2

NSRE :

Nutrient-sensing response element

OA:

Oleic acid

ODC :

Ornithine decarboxylase

ONE :

4-oxo-(2E)-nonenal

OXPHOS:

Oxidative phosphorylation

PA:

Palmitic acid

PAHs:

Polyaromatic hydrocarbons

PD:

Protectin

PGH2:

Prostaglandin

PI3K:

Phosphatidylinositol-3-kinase

PLs:

Phospholipids

PMRS:

Plasma membrane redox system

PPAR:

Peroxisome proliferator-activated receptor

PUFA:

Polyunsaturated fatty acids

RNS:

Reactive nitrogen species

ROI:

Reactive oxygen intermediates

ROS:

Reactive oxygen species

RSS:

Reactive sulfur species

Rv:

Resolvins

SDHA:

Succinate dehydrogenase subunit-A

SLs:

Sphingolipids

SOD:

Superoxide dismutase

SSBs/DSBs:

Single/double-strand breaks

TBARS:

Thiobarbituric acid reactive substances

TGs:

Triglycerides

TNFα:

Tumor necrosis factor

TX:

Thromboxane

UCP:

Uncoupler protein

VA:

Vaccenic acid

XO:

Xanthine oxidase

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Author information

Authors and Affiliations

  1. Department of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli, Tamil Nadu, India

    Daniel Andrew M. Gideon

  2. Department of Medicine, University of Arizona, Tucson, AZ, USA

    Joel James

Authors
  1. Daniel Andrew M. Gideon
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  2. Joel James
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Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysic, University of Kalyani Department of Biochemistry and Biophysic, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Dept of Veterinary Pathobiology, University of Missouri, College Vet, Columbia, MO, USA

    Bimal K Ray

  3. Saroj Gupta Cancer Centre & Research Ins, Kolkata, India

    Sushanta Roychowdhury

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Gideon, D.A.M., James, J. (2021). Assessing the Contributions of Lipid Profile and Oxidative Lipid Damage to Carcinogenesis. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_185-1

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  • DOI: https://doi.org/10.1007/978-981-15-4501-6_185-1

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  • Print ISBN: 978-981-15-4501-6

  • Online ISBN: 978-981-15-4501-6

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