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Omega-3 Fatty Acids in Cancer: Insight into the Mechanism of Actions in Preclinical Cancer Models

  • Asavari A. Joshi
  • Mahabaleshwar V. Hegde
  • Sharad P. Adekar
Chapter

Abstract

Worldwide, the incidences of cancer are rising. Various environmental and genetic factors are predisposing individuals to cancer. Majority of these factors result in upregulation of pro-survival pathways, downregulation of tumor suppressors, and chronic inflammation. The ratio of w-6/w-3 polyunsaturated fatty acids (PUFAs) plays very crucial role in the initiation and progression of cancer. Low w-6/w-3 PUFA ratio has been shown beneficial in managing the hallmarks of cancer cell. Enormous data from cancer cell line and in vivo cancer models have given insight into the mechanisms underlying the anticancer effects of w-3 PUFAs. Here, we discussed major possible mechanisms for beneficial effects of w-3 PUFAs as evidenced by the preclinical in vitro cancer cell line models and in vivo models.

Keywords

Anticancer Lipid peroxidation Lipid rafts Eicosanoids Mitochondrial hyperpolarization Inflammation Apoptosis Metastasis Immunomodulation Fat-1 transgenic mouse model 

Abbreviations

ALX/FPR2

Lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2)

AP1

Activator protein 1

Bak

Bcl-2 homologous antagonist killer

BAX

Bcl-2-associated X protein

bcl-2

B-cell lymphoma 2

BCRP

Breast cancer resistance protein

bFGF

Basic fibroblast growth factor

BLT1

Leukotriene B4 receptor 1

Bv8

Prokineticin-2

CCL2

Chemokine (C–C motif) ligand 2

CCR5

C–C chemokine receptor type 5

ChemR23

Chemerin Receptor 23

COX

Cyclooxygenase

cPLA2

Cytosolic phospholipases A2

CXCL12

C–X–C motif chemokine 12

CYP450

Cytochrome P450

DCA

Dichloroacetate

DHA

Docosahexaenoic acid

DRM

Detergent-resistant membranes

EDPs

Epoxydocosapentaenoic acids

EETs

Epoxyeicosatrienoic acids

EEQs

Epoxyeicosatetraenoic acids

eFoX

Electrophile oxo-derivative

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

EGFR

Epithelial growth factor receptor

EPA

Eicosapentaenoic acid

EMT

Epithelial–mesenchymal transition

ER

Estrogen receptor

ETC

Electron transport chain

FA

Fatty acids

FASN

Fatty acid synthase

GPR120

G protein-coupled receptor 120

GPR32

G protein-coupled receptor 32

HEPEs

Hydroxyeicosapentaenoic acids

HER-2

Human epidermal growth factor receptor 2

HETEs

Hydroxyeicosatetraenoic acids

HGF

Hepatocyte growth factor

HIF

Hypoxia-inducible factor

HMGB1

High-mobility group box-1

HMGCoAR

3-hydroxy-3methylglutaryl-coenzyme A reductase

HUVECs

Human umbilical vein endothelial cells

HEPE

Hydroxyeicosapentaenoic acid

ICAM-1

Intercellular adhesion molecule 1

IGF-1R

Insulin-like growth factor 1 receptor

IL-1

Interleukin 1

IL-10

Interleukin 10

IL-6

Interleukin 6

iNOS

Inducible nitric oxide synthase

JNK

c-Jun N-terminal kinas

LA

Linoleic acid

LC-PUFA

Long-chain polyunsaturated fatty acid

LOX

Lipoxygenase

LTB4

Leukotriene B4

MAPKs

Mitogen-activated protein kinases

MCP-1

Monocyte chemotactic protein 1

M-CSF

Macrophage colony-stimulating factor

MMPs

Matrix metalloproteases

MRPs

Multidrug resistance-related proteins

MTP

Mitochondrial permeability transition

w-3

Omega-3

w-6

Omega-6

NF-kB

Nuclear factor-kappaB

NO

Nitric oxide

nrf2

Nuclear factor (erythroid-derived 2)-like 2

OSM

Oncostatin M

PCNA

Proliferating cell nuclear antigen

PDGF

Platelet-derived growth factor

PDH

Pyruvate dehydrogenase

PDK

Pyruvate dehydrogenase kinase

Pgp/ABCB1

P-glycoprotein/ATP-binding cassette subfamily B member

PI3K/mTOR

Phosphoinositide 3-kinase/mammalian target for rapamycin

PKC

Protein kinase C

PMN

Polymorphonuclear

PPARγ

Peroxisome proliferator-activated receptors

PPREs

PPAR response elements

PUFA

Polyunsaturated fatty acids

ROS

Reactive oxygen species

RXR

Retinoid X receptor

SOCI

Store-operated calcium influx

SREBP1

Sterol regulatory element-binding protein-1

STAT-3

Signal transducer and activator of transcription 3

TAK1

Transforming growth factor β-activated kinase-1

TAM

Tumor-associated macrophages

TAN

Tumor-associated neutrophils

TCA cycle

Tricarboxylic acid cycle

TGF-β

Transforming growth factor-beta

TNF α

Tumor necrosis factor-alpha

VCAM-1

Vascular cell adhesion protein 1

VEGF

Vascular endothelial growth factor

ALA

α-linolenic acid

Notes

Acknowledgments

Authors would like to thank Mr. Aniket Mali for the illustration in Fig. 12.1.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Asavari A. Joshi
    • 1
  • Mahabaleshwar V. Hegde
    • 1
  • Sharad P. Adekar
    • 2
  1. 1.Center for Nutrition Health and DiseaseIRSHA, Bharati Vidyapeeth Deemed UniversityPuneIndia
  2. 2.Western IRBPuyallupUSA

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