Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer (eBook)

Contents 5
Contributors 7
Introduction: Omega-3 PUFAs, Why Do We Speak About Them? 9
Introduction 9
Chemistry and Metabolism of -3 PUFAs 10
Intracellular Metabolism of -3 PUFAs and Competition with Arachidonic Acid 11
Dietary Sources and Bioavailability of -3 PUFAs 13
Beneficial Effects of -3 PUFAs on Human Health 15
Studies on -3 PUFAs and Cancer: Discrepancies Between the results of In Vitro and In Vivo Experimental Studies and Human Observational Studies 16
Effect of -3 PUFAs in Cancer: Organization of the Present Book 17
References 18
Part I Possible Mechanisms 22
1 Possible Mechanisms of -3 PUFA Anti-tumour Action 23
1.1 Introduction 24
1.2 Cell Death 25
1.2.1 Non-apoptotic Forms of Cell Death 25
1.2.2 Apoptosis 26
1.2.2.1 Extrinsic Pathway of Apoptosis 27
1.2.2.2 Intrinsic Pathway of Apoptosis 27
1.2.2.3 Activation of Caspases 28
1.2.2.4 Disruptions of the Extrinsic and Intrinsic Pathways in Cancer Cells 28
1.2.3 -3 Fatty Acids and Their Effects on Apoptosis 29
1.2.3.1 -3 PUFA-Induced Changes in Membrane Fluidity, Structure, and Composition in Tumour Cells 29
1.2.3.2 Effect of -3 PUFAs on Enzyme and Receptor Activity and Location 32
1.2.3.3 Effect of -3 PUFAs on the Network of Lipid Molecular Second Messengers 33
1.2.3.4 Molecules and Genes Involved in the Regulation of Inflammation 33
1.2.4 Conclusions: -3 PUFAs and Their Effects on Cell Death and Apoptosis 35
1.3 Cell Growth 36
1.3.1 Growth Factor Pathways 36
1.3.1.1 Epidermal Growth Factor Receptor and Its Role in Tumour Growth 36
1.3.1.2 Her-2 Receptor 37
1.3.1.3 Effect of -3 PUFAs on the EGF Proteins 37
1.3.1.4 Insulin-Like Growth Factors 38
1.3.1.5 Effect of -3 PUFAs on IGF 39
1.3.2 Effects of -3 PUFAs on Cell Proliferation Signals 40
1.3.2.1 Cyclins and Associated Proteins 40
1.3.2.2 TCF-Catenin and Effects on VEGF, MMP-7, and MT1-MMP 41
1.3.3 Effects of -3 PUFAs on Membrane-Generated Lipid Compounds 42
1.3.3.1 Eicosanoids 42
1.3.3.2 ROS and Products of Lipid Peroxidation 43
1.3.3.3 Other Membrane-Generated Lipids Involved in Signalling 44
1.3.4 Effects of -3 PUFAs on Transcription Factors 44
1.3.5 Effects of -3 PUFAs on Ras and Protein Kinase C 45
1.3.6 Summary of the Effects of -3 PUFAs on Tumour Cell Growth 46
1.4 Conclusions 46
References 47
Part II boldCanada-3 PUFAs and Colon Cancer 59
2 -3 PUFAs and Colon Cancer: Epidemiological Studies 60
2.1 Introduction 9
2.1.1 Definitions and Sources of Fish 61
2.1.2 Composition of Fish 61
2.1.3 Consumption of Fish 61
2.2 Evidence from Epidemiological Studies 15
2.2.1 Ecological Studies 62
2.2.2 Case--Control Studies 62
2.2.3 Cohort Studies 79
2.2.4 Randomized Controlled Trials (RCT) 80
2.3 Comprehensive Assessment 80
2.4 Discussion 80
2.4.1 Reasons for Inconsistent Results in Epidemiological Studies 80
2.4.1.1 The Relationship Between Serum -3 PUFA Levels and Fish Intake by FFQ 80
2.4.1.2 Portion Size and Fish Type in Dietary Assessment 81
2.4.1.3 Generation of Carcinogenic Substances by Cooking Fish at a High Temperature 81
2.4.1.4 Definition of Fish 81
2.4.2 Subsite-Specific Analysis 81
2.5 Conclusions 81
References 82
3 -3 PUFAs and Colon Cancer: Experimental Studies and Human Interventional Trials 86
3.1 Introduction 86
3.2 Experimental Studies 87
3.2.1 Animal Studies 87
3.2.1.1 Chemically Induced Colon Carcinogenesis in Rat Models 87
3.2.1.2 Tumor Cells Transplanted into Animals 91
3.2.1.3 Genetic Models for the Induction of Colon Cancer 93
3.2.2 In Vitro Studies with Normal and Tumor Colonic Cells 94
3.2.3 In Vitro and In Vivo Combined Treatments with -3 PUFAs and Other Anti-neoplastic Agents 97
3.3 Interventional Trials 98
3.4 Conclusion 100
References 100
Part III boldItaly-3 PUFAs and Hormone-Related Cancers (Breast and Prostate) 109
4 -3 PUFAs and Breast Cancer: Epidemiological Studies 110
4.1 Introduction 110
4.2 Breast Cancer 111
4.3 EPA and DHA 111
4.4 Epidemiological Studies 112
4.4.1 Ecological Studies of Fish Consumption 112
4.4.2 Case--Control Studies 112
4.4.2.1 Fish Consumption 114
4.4.2.2 Long-Chain -3 PUFAs EPA and DHA 114
4.4.3 Prospective Cohort Studies 116
4.4.3.1 Fish Consumption 116
4.4.3.2 Long-Chain -3 PUFAs EPA and DHA 116
4.4.4 Fatty Acid Ratios and Breast Cancer 117
4.4.5 Short-Chain -3 PUFA -Linolenic Acid (ALA) 117
4.5 Discussion 118
References 120
5 -3 PUFAs and Prostate Cancer: Epidemiological Studies 125
5.1 Introduction 125
5.1.1 Prostate Cancer: Epidemiological Characteristics 125
5.1.2 -3 Polyunsaturated Fatty Acids (PUFAs): Biochemical and Nutritional Considerations 127
5.1.3 Studies Selection 128
5.2 ALA and Prostate Cancer 128
5.2.1 Ecological Studies 148
5.2.2 Case--Control Studies Based on Dietary Questionnaires 148
5.2.3 Cohort Studies Based on Dietary Questionnaires 149
5.2.4 Case--Control or Cross-Sectional Studies Based on Biomarkers 150
5.2.5 Case--Control Studies Nested Within Cohorts, Based on Biomarkers 150
5.2.6 Discussion 151
5.3 Long-Chain -3 PUFAs and Prostate Cancer 153
5.3.1 Ecological Studies 153
5.3.2 Case--Control Studies Based on Dietary Questionnaires 154
5.3.3 Cohort Studies Based on Dietary Questionnaires 155
5.3.4 Case--Control Studies Based on Biomarkers 156
5.3.5 Case--Control Studies Nested in Cohorts Based on Biomarkers 157
5.3.6 Interaction of Long-Chain -3 PUFAs with COX-2 Polymorphisms 157
5.3.7 Discussion 158
5.4 Concluding Remarks 159
References 160
6 -3 PUFAs: Interventional Trials for the Prevention and Treatment of Breast and Prostate Cancer 165
6.1 Introduction 166
6.2 Prevention and Treatment of Prostate Cancer with -3 PUFAs 172
6.3 Prevention and Treatment of Breast Cancer with -3 PUFAs 175
6.4 Nutritional Support and Immunomodulation of Cancer Patients with -3 PUFAs 178
6.5 Conclusions 179
References 180
7 -3 PUFAs, Breast and Prostate Cancer: Experimental Studies 183
7.1 Introduction 184
7.2 Fatty Acid Sources and Metabolism 184
7.3 PUFA Studies in Animals 185
7.3.1 PUFAs in Animal Breast Cancer 185
7.3.2 PUFAs in Animal Prostate Cancer 187
7.4 Mechanisms for the Anti-cancer Activity of PUFAs 189
7.4.1 PUFA Mechanisms in Breast Cancer 189
7.4.2 PUFA Mechanisms in Prostate Cancer 193
7.5 Conclusions 195
References 196
Part IV boldUSA-3 PUFAs and Other Cancers 205
8 -3 PUFAs and Other Cancers 206
8.1 -3 Polyunsaturated Fatty Acids (PUFAs) and Pancreatic Cancer 206
8.2 - 3 PUFAs and Lung Cancer 210
8.3 -3 PUFAs and Skin Cancer 214
8.3.1 Nonmelanoma Skin Cancer (NMSC) 214
8.3.2 Melanoma Skin Cancer 216
8.4 -3 PUFAs and Cholangiocarcinoma 217
8.5 -3 PUFAs and Leukemia 219
8.6 Conclusions 222
References 222
9 The Influence of -3 PUFAs on Chemo- or Radiation Therapy for Cancer 233
9.1 Introduction 233
9.2 In Vitro Studies Using -3 PUFAs and Chemotherapeutic Agents 234
9.3 Mechanisms of Action for Increased Sensitivity to Drug 234
9.3.1 Oxidative Stress 235
9.3.2 Altered Membrane Permeability, Fluidity, or Drug Uptake 235
9.3.3 Changes in Apoptosis Susceptibility 236
9.3.4 Modulation of the Transcription Factor, Nuclear Factor Kappa B (NF- 0 B) 236
9.3.5 Altered Activity of Membrane-Associated Receptors 237
9.3.6 Altered Cell Signaling 237
9.3.7 In Vivo Studies on Enhanced Chemotherapy with -3 PUFAs 237
9.4 -3 PUFAs and Radiation Therapy 238
9.5 -3 PUFAs in Clinical Trials 239
References 240
10 -3 PUFAs and Cachexia 245
10.1 What Is Cachexia? 245
10.2 Anorexia and Cachexia 246
10.3 Mechanism of Loss of Adipose Tissue in Cachexia 247
10.4 Possible Mediators of Fat Loss in Cachexia 247
10.5 Mechanism of Loss of Skeletal Muscle in Cachexia 248
10.6 Effect of -3 PUFAs on Experimental Cachexia Models 250
10.7 Mechanism of Effect of -3 PUFAs on Adipose Tissue 250
10.8 Mechanism of Effect of -3 PUFAs on Skeletal Muscle 251
10.9 Clinical Studies of -3 PUFAs in Cachexia 253
10.10 Conclusion 256
References 257
Index 261