Nutraceuticals and Cancer Signaling: Clinical Aspects and Mode of Action (Food Bioactive Ingredients)

Today's consumers are looking for food products with health-promoting roles in addition to nutritional benefits. With current research showing that nutraceuticals and functional foods rich in specific bioactives may have chemopreventative effects, these products are increasingly popular. However, while much in the literature supports the health-promoting features of these foods, few texts focus on their bioactive agents and their mode of action in cancer signaling. Nutraceuticals and Cancer Signalling: Clinical Aspects and Mode of Action explains the link between nutraceuticals and cancer in terms of clinical trials and modes of action. This book gives an overview of common cancers and their mechanisms, and the most common functional foods and their bioactive components. Individual chapters focus on specific functional foods--including tomatoes, garlic, honey, tea, yoghurt, and many more--their prominent bioactive compounds, and their mode of action in cancer signaling and chemoprevention. Recent findings on cancer-prevention roles of different vitamins and minerals are also discussed. For food scientists, nutritionists, and pharmaceutical experts looking to understand how functional foods can play a role in fighting cancer, this text serves as a one-stop reference. Preface Contents Part I: An Overview of Cancer and Its Mechanisms Chapter 1: A Brief Overview of Cancer, Its Mechanisms, and Prevention Methods 1 Cancer Over Time 2 Cancer Prevention 3 Treatment of Cancer 4 Natural Food Compounds and Cancer 5 Remarking Conclusions References Chapter 2: Mechanisms Involved in Carcinogenesis 1 Introduction 2 Phases of Carcinogenesis: Initiation, Promotion, and Progression 2.1 Initiation 2.2 Promotion 2.3 Progression 3 Mechanisms of Carcinogenesis 3.1 Oncogenes Activation 3.2 Tumor Suppressor Gene Inactivation 3.3 Association Between Infectious Agents and Carcinogenesis 3.3.1 Oncogenic Virus DNA Tumor Virus RNA Tumor Virus 3.3.2 Oncogenic Bacteria 3.3.3 Oncogenic Parasites 3.3.4 Oncogenic Fungi 3.4 Involvement of MicroRNA in Cancer 3.5 Role of Epigenetics in Cancer 3.5.1 DNA Methylation 3.5.2 Histone Modifications 3.5.3 Dysregulation of miRNAs Expression 4 Conclusion References Part II: Functional Foods/Nutraceuticals as Chemo Preventive Agents Chapter 3: Tomato (Lycopene and β-Carotene) and Cancer 1 Introduction 2 Tomatoes: Botanical Aspect, Composition and Main Properties 3 Carotenoids 4 Lycopene 4.1 Chemistry 4.2 Bioavailability 4.3 Biological Activities and Modes of Action 5 β-Carotene 5.1 Chemistry 5.2 Bioavailability 5.3 Biological Activities and Modes of Action 6 Epidemiologic Studies 7 Animal Studies 8 Human Clinical Trials 9 Limitations of Cancer Studies and Future Trends 10 Conclusion and Future Trends References Chapter 4: Essential Oils from Aromatic Plants in Cancer Prevention and Treatment 1 Introduction 2 Chemical Composition of Essential Oils 3 Main Studied Essential Oils 3.1 Essential Oils from Boswellia spp. 3.2 Essential Oils from Cinnamomum spp. 3.3 Essential Oils from Citrus spp. 3.4 Essential Oils from Curcuma spp. 3.4.1 Curcuma longa 3.4.2 Curcuma zedoary 3.5 Essential Oils from Cymbopogon spp. 3.5.1 Cymbopogon citratus 3.6 Essential Oils from Lavandula spp. 3.7 Essential Oils from Origanum spp. 3.7.1 Origanum vulgare 3.7.2 Origanum majorana 3.8 Essential Oils from Pinus spp. 3.8.1 Pinus densiflora 3.8.2 Pinus koraiensis 3.9 Essential Oils from Salvia spp. 3.10 Essential Oils from Thymus spp. 3.11 Essential Oils from Zataria multiflora 4 Concluding Remarks References Chapter 5: Bee Propolis (Caffeic Acid Phenethyl Ester) Against Cancer 1 Introduction 2 Chemistry of Bee Propolis 3 Cape Bioavailability and Metabolism 4 Biological Activities of Bee Propolis 4.1 Antibacterial Activity 4.2 Antiviral Activity 4.3 Antifungal Activity 4.4 Antiprotozoal and Antiparasitic Activity 4.5 Anti-inflammatory Activity 5 Neuroprotective and Hepatoprotective Properties of Bee Propolis 6 Anti-tumour Properties of Bee Propolis 6.1 Effects of Propolis on Angiogenesis, Metastasis and Tumour Invasion 6.2 Effect of Propolis Against the Toxicity of Drugs 7 Nutraceutical Usage of Bee Propolis 8 Conclusion References Chapter 6: Brown Algae (Fucoxanthin) Against Cancer 1 Introduction 2 Biological Activities of Fucoxanthin 2.1 Cardiovascular Protection 2.2 Anti-obesity Effect 2.3 Hepatoprotective Effect 2.4 Anti-diabetic Effect 2.5 Anti-inflammatory Effect 2.6 Antioxidative Effect 2.7 Anti-bacterial Effect 3 Anticancer Effects 4 Molecular Mechanisms of Fucoxanthin for G1/G2 Arrest, Apoptosis, Autophagy and Metastasis Inhibition 4.1 G1 Cell Cycle Arrest in Tumor Cells 4.2 Apoptosis 5 Fucoxanthin Application as a Functional Food 6 Strategies to Cope with Unfavorable Reactions in Functional Food 7 Conclusion References Chapter 7: Cruciferous Vegetables (Indole-3-Carbinol, Isothiocyanates) Against Cancer 1 Introduction 2 Cruciferous Vegetables 2.1 Botanical Features 2.2 Chemistry of Bioactive Compounds 2.2.1 Glucosinolates 2.3 Metabolism of Bioactive Compounds 3 Cruciferous Vegetables and Cancer 4 Main Putative Anticancer Mechanisms of Action 4.1 Cell Cycle Arrest 4.2 Apoptosis 4.3 Signalling Pathways Involving Akt 4.4 AHR Signalling Pathway 4.5 Carcinogen Metabolising Enzymes 4.6 Epigenetic Effects 5 Conclusion References Chapter 8: Crustacea (Carotenoids Namely Astaxanthins) Against Cancer 1 Introduction 2 Chemistry of Astaxanthin 3 Isomerization of Trans-astaxanthin 4 Bioavailability and Safety of Astaxanthin 5 Potential Health-Promoting Effects of Astaxanthin 5.1 Anti-inflammatory Activity 5.2 Anti-apoptotic Activity 5.3 Antioxidant Activity 5.4 Neuroprotective Activity 5.5 Effect on Bone 5.6 Effect on Immune System 5.7 Effect on Skin Health 5.8 Effect on Cardiovascular Health 5.9 Effect on Sports Performance 5.10 Effect on Blood Glucose Control and Type 2 Diabetes Mellitus 5.11 Anti-cancer Activity 5.11.1 Astaxanthin and Its Mechanisms of Anti-cancer Activity 5.11.2 Anti-proliferation of Cells 5.11.3 Apoptosis 5.12 Anti-oxidation 5.13 Anti-inflammation 5.14 Invasion and Migration 5.15 Gap Junctional Intracellular Communication (GJIC) 5.16 Molecular Targets of Astaxanthin 5.16.1 NF-kB 5.16.2 Janus Kinase/Signal Transducers and Activators of Transcription-3 (JAK/STAT-3) 5.16.3 PI3K/AKT 5.16.4 MAPKs 5.16.5 Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) 5.16.6 NF-E2-Related Factor 2 (Nrf2) 5.17 Effects on Kidney Function 5.18 Effects on Eye Health 5.19 Effects on Fertility 5.20 Effects on Smokers 5.21 Effect on Preeclampsia 5.22 Angiogenesis 6 Conclusion References Chapter 9: Curcuma and Breast Cancer: A Focus on Cell Signaling Pathways 1 Introduction 2 Phytoconstituents of Curcuma 2.1 Terpenoids 2.1.1 Monoterpenes 2.1.2 Sesqueterpenes 2.2 Beta-diketones 3 Anti-breast Cancer Activity of Genus Curcuma 3.1 Curcuma and Cell Cycle Arrest 3.2 Curcuma and Apoptosis 3.2.1 Curcuma and p53 3.2.2 Curcuma and NF-κB 3.2.3 Curcuma and STAT3 Pathway 3.2.4 Curcuma and Wnt Signaling Pathway 3.2.5 Curcuma and MAPK Pathway 3.2.6 Curcuma and PI3K/Akt/mTOR Pathway 4 Conclusions References Chapter 10: Fruits and Vegetables in Cancer 1 Introduction 2 Quercetin 2.1 Quercetin and Colorectal Cancer 2.2 Quercetin and Breast Cancer 2.3 Quercetin and Prostate Cancer 2.4 Quercetin and Gastric Cancer 2.5 Quercetin and Oral Cancer 2.6 Quercetin and Other Cancers 3 Resveratrol 3.1 Resveratrol and Colorectal Cancer 3.2 Resveratrol and Breast Cancer 3.3 Resveratrol and Prostate Cancer 3.4 Resveratrol and Other Cancers 4 Carotenoids 4.1 Lycopene and Prostate Cancer 4.2 Lycopene and Breast Cancer 4.3 Lycopene and Ovarian Cancer 4.4 Other Carotenoids and Cancers 5 Dietary Fibers 5.1 Lignans and Breast Cancer 5.2 Lignans and Gastrointestinal Cancers 5.3 Lignans and Lung Cancer 5.4 Lignans and Other Cancers 6 Evidences in Focus 7 Final Remarks References Chapter 11: Garlic: Allyl Sulfur Compounds and Cancer Prevention 1 Introduction 2 Organosulphur Compounds (OSCs) 2.1 Water-Soluble Organosulphur Compounds: S-Allyl Cysteine (SAC), S-Allylmercaptocysteine (SAMC) 2.2 Oil-Soluble Organosulphur Compounds 3 Cancer Chemopreventive Effects of Organosulfur Compounds of Garlic 3.1 In Vitro Studies 3.2 In Vivo Studies 4 Epidemiological Studies 5 Mechanisms of Action 5.1 Stimulation of Detoxification Enzymes 5.2 Cell Protection from Oxidative Stress 5.3 Induction of Cell Death and Cell Cycle Arrest 5.4 Immune System Enhancement 5.5 Epigenetic Mechanisms 6 Future Directions for Research on the Anticancer Effects of Garlic References Chapter 12: Ginger (Gingerols and 6-Shogaol) Against Cancer 1 Introduction 2 Ginger in Cancer Treatment and Prevention 2.1 In Vitro Cytotoxicity Studies 2.2 In Vivo Anticancer Studies and Mechanism of Action 3 Anticancer Mechanisms of Ginger 3.1 MAPK (Mitogen-Activated Protein Kinase) Signaling 3.2 PI3K/Akt/mTOR Signaling 3.3 JAK (Janus Kinase)/STAT (Signal Transducer and Activator of Transcription) 3.4 Activator Protein-1 (AP-1) Transcription Factor 3.5 TNF-Related Apoptosis-Inducing Ligand (TRAIL) Signaling 3.6 NF-kB Signaling Pathway 4 Clinical Trials 5 Conclusion References Chapter 13: Saffron (Crocins) Against Cancer 1 Introduction 2 Composition of Saffron 3 Pharmacology of Saffron 4 Anticancer Molecular Mechanisms of Saffron and Its Active Ingredients 4.1 Antioxidant Effect 4.2 Apoptotic and Tumor-Suppressive Effects 4.3 Anti-inflammatory Effects 4.4 Regulation of Topoisomerase Activity 5 Saffron and Cancer 5.1 Breast Cancer 5.2 Bladder Cancer 5.3 Cervical Cancer 5.4 Colon Cancer 5.5 Esophageal Cancer 5.6 Gastric Cancer 5.7 Glioblastoma 5.8 Head and Neck Cancer 5.9 Leukemia 5.10 Liver Cancer 5.11 Lung Cancer 5.12 Osteosarcoma 5.13 Ovarian Cancer 5.14 Pancreatic Cancer 5.15 Prostate Cancer 5.16 Retinoblastoma 5.17 Rhabdomyosarcoma 5.18 Skin Cancer 5.19 Tongue Squamous 6 Saffron Loaded-Nanoparticles for Cancer Therapy 7 Saffron in Combination with Cancer Chemotherapeutics 8 Saffron Protective Effects Against Anticancer Drugs Toxicity 9 Conclusions and Future Directions References Chapter 14: Olive Leaf (Oleuropein) and Its Role in Cancer: Therapeutic Updates 1 Introduction 2 Traditional Uses of Olive 3 Pharmacological Study of Olive Plant 4 Pharmacological Effects of Olive Leaf 4.1 Hypoglycemic Effect 4.2 Hypertensive Effect 4.3 Cardiovascular Effect 4.4 Antioxidant Effect 4.5 Anti-inflammatory Effect 4.6 Antihyperipidemic Effect 4.7 Antiviral Effect 5 Phytochemical Profile of Olive Tree 5.1 Olive Leaf Polyphenols 5.1.1 Oleuropein 5.1.2 Hydroxytyrosol (HT) 5.1.3 Hdroxytyrosol Derivatives 5.2 In Vivo Absorption, Metabolization and Excretion of Oleuropein and Its Derivatives 6 Anticancer Activity of Olive Leaf Bioactive Compounds (Oleuropein and Related Compounds) 6.1 Prostate Cancer 6.2 Cervical Cancer 6.3 Lung Cancer 6.4 Thyroid Cancer 6.5 Gloiblastoma 6.6 Neuroblastoma 6.7 Skin Cancer 6.8 Antitumor Agent 6.9 Leukemia 6.10 Pancreatic Cancer 7 Mechanisms Involved in Cancer Treatment by Olive Leaves (Oleuropein and Its Derivatives) 8 Conclusion References Chapter 15: Honey Against Cancer 1 Introduction 2 Chemical Composition of Honey 3 Types of Honey and Their Synthetic Analogues 3.1 Acacia Honey 3.2 Alfalfa Honey 3.3 Avocado Honey 3.4 Basswood Honey 3.5 Blueberry Honey 3.6 Buckwheat Honey 3.7 Clover Honey 3.8 Eucalyptus Honey 3.9 Fireweed Honey 3.10 Manuka Honey 3.11 Orangeblossom Honey 3.12 Sourwood Honey 3.13 Sage Honey 3.14 Tupelo Honey 4 Synthetic Analogues 5 Anticancer Activity of Honey 5.1 Honey and Its Antioxidant Activity 5.2 Honey and Its Apoptotic Activity 5.3 Honey and Its Anti-proliferative Activity 5.4 Tumor Necrosis Factor (TNF) 5.5 Honey and Its Anti-inflammatory and Immunomodulatory Activities 5.6 Honey and Its Antimutagenic Activity 6 Synergistic Effects of Honey 6.1 Synergistic Effect with Substances That Produces Hypoglycemia 6.2 Synergistic Effect with Substances That Produces Antioxidant Effect 6.3 Synergistic Effect with Substances That Produces Antihypertensive Effect 7 Clinical Trials 8 Conclusion References Chapter 16: Soybeans and Phytoestrogen Rich Foods (Genistein, Daidzein) Against Cancer 1 Introduction 2 Phytoestrogens Rich Foods 3 Chemical Properties of Isoflavones 4 Metabolism of Soy-Isoflavonoids 5 Molecular Targets of Isoflavonoids 6 In Vitro Studies 6.1 Breast Cancer 6.2 Prostate Cancer 7 Observational and Clinical Trials 7.1 Breast Cancer 7.2 Prostate Cancer 8 Conclusion References Chapter 17: Tea (Catechins Including (−)-Epigallocatechin-3-gallate) and Cancer 1 Introduction 2 Chemical Aspects of Tea Catechins 3 Catechins: Bioavailability and Metabolism 4 Therapeutic Potential of Catechins 5 Catechins and Cancer 5.1 Lung Cancer 5.2 Colorectal Cancer 5.3 Breast Cancer 5.4 Prostate Cancer 5.5 Gastric Cancer 6 Molecular Mechanisms of Anticancer Activity of Tea Catechins 6.1 Induction of Apoptosis 6.2 Autophagy 6.3 PI3K-AKT Signaling Pathway 6.4 Receptor Tyrosinase Kinase Inhibitory Activity 6.5 Epigenetic Regulation 6.6 Immune Check Point Inhibitory Activity 6.7 Anti-mutagenic Activity 6.8 Antioxidant Activity 7 Combination Therapy with Other Anticancer Drugs 8 Conclusions References Chapter 18: Probiotics and Cancer 1 Introduction 2 Sources of Probiotics 2.1 Chicken Cecum 2.2 Dairy Products 2.3 Fermented Milk 2.4 Goat Milk 2.5 Kefir 2.6 Kimchi 2.7 KIOM-MA 2.8 Kombucha 2.9 Kumys 2.10 Noni 2.11 Probiotics in Human Breast Milk 2.12 Soymilk 2.13 Utonga Kupsu 2.14 Yogurt 3 Mechanisms of Action of Probiotics in Cancer 3.1 Immunomodulatory Effects 3.2 Modulation of Inflammatory Response 3.3 Antioxidant Activity 3.4 Antiproliferative and Apoptotic Effect 3.5 Antiangiogenesis 3.6 Anticarcinogenicity 3.7 Production of Short-Chain Fatty Acids 3.8 Enhancement of Barrier Function 3.9 Inhibition of the Enzymatic Activity of Pathogenic Bacteria 4 Effects of Probiotics in Cancer Prophylaxis and Treatment 4.1 Breast Cancer 4.1.1 In Vitro Studies 4.1.2 Animal Studies 4.1.3 Human Studies 4.2 Cervical Cancer 4.2.1 In Vitro Studies 4.2.2 Human Studies 4.3 Colorectal Cancer 4.3.1 In Vitro Studies 4.3.2 Animal Studies 4.3.3 Human Studies 4.4 Gastric Cancer 4.4.1 In Vitro Studies 4.4.2 Human Study 4.5 Leukemia 4.5.1 In Vitro Studies 4.5.2 Animal Studies 4.6 Liver Cancer 4.6.1 In Vitro Studies 4.6.2 Animal Studies 4.6.3 Human Study 4.7 Lung Cancer 4.7.1 In Vitro Studies 4.7.2 Animal Studies 4.7.3 Human Study 4.8 Oral Cancer 4.8.1 In Vitro Studies 4.9 Pancreatic Cancer 4.9.1 Animal Studies 4.10 Melanoma 4.10.1 Animal Studies 5 Safety of Probiotics in Cancer Treatment 6 Conclusion References Part III: The Role of Nutrients in the Prevention of Cancer Chapter 19: Vitamins (C, D and E) Against Cancer 1 Introduction 2 Structural and Biological Characteristics of Vitamins 3 Vitamins C, D and E in Cancer Care 3.1 Mode of Action that Relates Vitamins to Cancer 3.2 Clinical Evidence Associating Vitamins C, D and E with Cancer 4 Conclusions References Chapter 20: Minerals (Namely Selenium) and Cancer 1 Introduction 2 Nutritional Aspects 3 Selenium Compounds 4 Relation of Selenium and Cancer 5 Selenium and Cancer Prevention 6 Selenium in Cancer Therapy 7 Conclusions References Chapter 21: Dietary Fibers/Beta-Glucan and Cancer 1 Introduction 2 Beta-Glucans 2.1 Pharmacodynamics and Pharmacokinetics of Beta Glucans 2.2 Beta-Glucan as an Immunomodulating Agent 3 Beta Glucans and Cancer 3.1 Cancer 3.1.1 Major Signaling Pathways Involved in Carcinogenesis 3.1.2 Protein Kinases and Signal Transduction 3.1.3 MAP Kinase Signal Transduction Pathway 3.1.4 Ras/Raf/MEK/ERK Signal Transduction Pathway 3.1.5 PI-3 Kinase/Protein Kinase B Signal Transduction Pathway 3.1.6 STAT Signal Transduction Pathways 3.2 Anti-Cancer Effects of Beta-Glucans 4 Conclusion and Future Perspectives References Chapter 22: Omega-3 Polyunsaturated Fatty Acids and Cancer 1 Introduction 2 Omega-3 and Omega-6 Fatty Acid Metabolism in Human 3 Recommended Daily Doses of Omega-3 Fatty Acids 4 Sources and Bioavailability of Omega-3 5 Health Benefits of Omega-3 6 Cancer and Omega-3 6.1 Colorectal Cancers and Omega-3 6.2 Prostate Cancer and Omega-3 6.3 Gastric Cancers and Omega-3 6.4 Leukemia and Omega-3 6.5 Pancreatic Cancer and Omega-3 6.6 Lung Cancer and Omega-3 6.7 Breast Cancer and Omega-3 6.8 Head and Neck Cancers and Omega-3 7 Clinical Trials 8 Conclusion References Index