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Possible Mechanisms of ω-3 PUFA Anti-tumour Action

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Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer

Part of the book series: Diet and Cancer ((DICA,volume 1))

Abstract

Cancer is a disease characterized by an imbalance between cell division and cell death. Although the molecular mechanisms which account for the biological effects of the ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs) are not completely understood, there is considerable evidence from animal tumours and human cell lines that providing docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) will both increase apoptotic and other death pathways and decrease cell growth. ω-3 PUFAs appear to mediate these beneficial effects by affecting the expression and/or function of the lipids, proteins, and genes that regulate these processes. The current evidence supports a hypothesis that these anti-tumour effects are initiated by the ability of DHA and EPA to alter the lipid environment of the cell and in doing so modulate receptors, proteins, and lipid-derived signals originating from cell membranes. The evidence for the possible mechanisms for the beneficial effects of ω-3 PUFAs on tumour cell death and/or proliferation is reviewed in this chapter.

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Abbreviations

PUFA:

Polyunsaturated fatty acids

AA:

Arachidonic acid

ALA:

Alpha linolenic acid

AOM:

Azoxymethane

Apaf-1:

Apoptotic peptidase activating factor 1

Bid:

Bcl-2 interacting domain

CDK:

Cyclin-dependent kinase

CDKI:

CDK inhibitors

COX-1 and -2:

Cyclooxygenase 1 and 2

DAG:

Diacylglycerol

DHA:

Docosahexaenoic acid

DISC:

Death-inducing signalling complex

DR:

Death receptors

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EPA:

Eicosapentaenoic acid

FLIP:

FLICE-inhibitory protein

GRB2:

Growth factor receptor-bound protein

IAP:

Inhibitor of apoptosis proteins

IGF:

Insulin-like growth factor

IGFBP:

IGF-binding protein

IP3:

Inositol (1,4,5) triphosphate

IRS:

Insulin receptor substrates

LA:

Linoleic acid

LOX:

Lipoxygenase

MAPK:

Mitogen-activated protein kinase

MMPs:

Matrix metalloproteinases

NFκB:

Nuclear factor κB

PGE2 :

Prostaglandin E2

PI3K:

Phosphatidylinositol-3-kinase

PIP2:

Phosphatidylinositol (4,5) bisphosphate

PIP3:

Phosphatidylinositol (3,4,5) triphosphate

PKC:

Protein kinase C

PLA2 and C:

Phospholipase 2 and C

PLC:

Phospholipase C

PPAR:

Peroxisome proliferator-activated receptors

pRB:

Phosphorylated RB

RB:

Retinoblastoma protein

ROS:

Reactive oxygen species

SHC:

Src homology and collagen domain

SMase:

Sphingomyelinase

SREBP:

Sterol regulatory element-binding protein

TNF:

Tumour necrosis factor

TNFR1:

TNF receptor 1

TRAIL-R1 and 2:

TNF-related apoptosis-inducing ligand receptor 1 and 2

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Acknowledgements

This research is supported by a grant from the Canadian Institute for Health Research. The authors wish to acknowledge the editorial help of K. Ruby in the preparation of the chapter.

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Authors and Affiliations

  1. Department of Oncology, University of Alberta, Edmonton, AB, Canada

    Michael B. Sawyer

  2. Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, 4-126A HRIF East, T6G 2E1, Edmonton, AB, Canada

    Catherine J. Field

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  1. Michael B. Sawyer
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  2. Catherine J. Field
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Correspondence to Catherine J. Field .

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  1. Istituto di Patologia Generale, Università Cattolica Sacro Cuore - Roma, Largo F. Vito 1, Roma, 00168, Italy

    Gabriella Calviello

  2. Istituto di Patologia Generale, Università Cattolica Sacro Cuore - Roma, Largo F. Vito 1, Roma, 00168, Italy

    Simona Serini

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Sawyer, M.B., Field, C.J. (2010). Possible Mechanisms of ω-3 PUFA Anti-tumour Action. In: Calviello, G., Serini, S. (eds) Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer. Diet and Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3579-0_1

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  • DOI: https://doi.org/10.1007/978-90-481-3579-0_1

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