Regional Analysis (eBook)

Front Cover 1
The Enzymes: Natural Products and Cancer Signaling: Isoprenoids, Polyphenols and Flavonoids 4
Copyright 5
Contents 6
Contributors 10
Preface 14
Chapter One: Introduction 16
References 21
Chapter Two: Perillyl Alcohol (Monoterpene Alcohol), Limonene 22
1. Introduction 23
2. Perillyl Alcohol 27
2.1. Perillyl Alcohol Mechanism of Action in Cancer Therapy and Pharmacokinetics 27
2.2. Perillyl Alcohol Biosafety and Adverse Effects in Clinical Application and Clinical Trials 30
3. Limonene 31
3.1. Limonene Pharmacokinetics 31
3.2. Limonene Anticancer Activity and Clinical Trials 33
3.3. Limonene Mechanisms of Action, Targets, and Clinical Applications 34
3.4. Limonene Biosafety and Adverse Effects 39
4. Concluding Remarks 40
Acknowledgment 41
References 41
Chapter Three: Ganoderic Acid and Lucidenic Acid (Triterpenoid) 48
1. Introduction 49
2. Lucidenic Acids and Ganoderic Acids from Ganoderma Species 50
2.1. The Sources of Lucidenic Acids and Ganoderic Acids 50
2.2. The Biosynthesis of Ganoderic Acids 51
2.3. Optimization of the Fermentation Process 56
3. Biological Functions of Lucidenic Acids and Ganoderic Acids 58
3.1. Cytotoxic and Apoptotic Effects 58
3.2. Cell Cycle Arrest 60
3.3. Anti-invasive Effect 60
3.4. Autophagy 63
3.5. Anti-inflammatory Effect 64
3.6. Antiosteoclastogenesis 64
3.7. Antiasthma 64
3.8. Antihepatitis B Activity 65
4. Pharmacokinetics of Ganoderic Acids 65
5. Conclusion 66
References 67
Chapter Four: Anticancer Effect and Molecular Targets of Saffron Carotenoids 72
1. Introduction 74
2. Anticancer Effect of Saffron and Its Carotenoids 74
3. Comparing the Efficacy of Crocetin, Crocin, and Other Components 75
4. Liposome Formulation of Saffron Compounds 79
5. Effect of Crocetin and Crocin on Macromolecule Synthesis and Structure 81
5.1. Effect on DNA, RNA, and Protein Synthesis 81
5.2. Protein Binding 82
6. Effects on Cell Cycle, Apoptosis, and Signaling Pathways 83
7. Role of Saffron Components on Chemoprevention 86
8. Molecular Mechanisms Involved in the Protective Effect of Saffron Components against Various Damages in Different Tissues 88
9. Antioxidant and Anti-inflammatory Effects of Saffron 91
10. Safety 93
11. Other Mechanisms 93
12. Conclusions 94
References 94
Chapter Five: Zerumbone from Ginger (Monoterpenoid) 102
1. Introduction 103
2. Characteristic Feature 104
3. Target Pathways by Zerumbone 104
3.1. Survival 104
3.1.1. Caspase Family 104
3.1.2. Bcl Family 104
3.1.3. c-FLIP 105
3.1.4. G2/M Cell Cycle 105
3.2. Proliferation 105
3.2.1. Cyclin B1/CDK1 105
3.2.2. Tumor Necrosis Factor 105
3.3. Invasion 105
3.4. Angiogenesis 105
4. Nuclear Factor-Kappa B 106
5. Future Perspectives 106
References 107
Chapter Six: Research Progress on Natural Triterpenoid Saponins in the Chemoprevention and Chemotherapy of Cancer 110
1. Introduction 111
2. Triterpenoid Saponins in the Prevention and Therapy of Cancers 112
3. Anticancer Properties and Molecular Mechanisms of Triterpenoid Saponins 113
3.1. Inhibition of Proliferation 113
3.2. Induction of Apoptosis and Autophagy 125
3.2.1. Apoptosis 125
3.2.2. Autophagy 128
3.3. Attenuation of Invasion and Metastasis 129
3.4. Inhibition of Angiogenesis 130
3.5. Anti-inflammatory Effects 132
3.6. Antioxidative Effects 133
3.7. Inhibition of Multidrug Resistance 133
3.8. Inhibition of CSCs 134
3.9. Modulation of MicroRNAs 135
4. Structure-Activity Relationships of Anticancer Activities of Triterpenoid Saponins 136
5. Clinical Studies 137
6. Summary and Perspectives 138
References 139
Chapter Seven: Neem Limonoids as Anticancer Agents: Modulation of Cancer Hallmarks and Oncogenic Signaling 146
1. Introduction 147
2. Cytotoxicity of Neem Limonoids 148
3. Neem Limonoids and Hallmarks of Cancer 151
3.1. Inhibition of Cell Proliferation 151
3.2. Apoptosis Induction 153
3.3. Effects on Tumor Invasion and Angiogenesis 154
3.4. Anti-Inflammatory Effects 154
3.5. Immunomodulatory Effects 154
3.6. Antioxidant Activity 155
4. Oncogenic Signaling 155
4.1. NF-.B Signaling 155
4.2. Wnt/ß-Catenin Signaling 156
4.3. PI3K/Akt Signaling 156
4.4. MAPK Signaling 157
4.5. JAK/STAT Signaling 157
5. Conclusions and Future Perspectives 157
References 158
Chapter Eight: Curcumin: A Potent Modulator of Multiple Enzymes in Multiple Cancers 164
1. Introduction 165
2. Structure-Activity Relationship of Curcumin 167
3. Curcumin Binds and Modulates Multiple Enzymes 168
3.1. Lipoxygenases 169
3.2. Cyclooxygenases 169
3.3. Xanthine Oxidase 170
3.4. Proteasomes 170
3.5. Ca2+-ATPase of Sarcoplasmic Reticulum 171
3.6. Matrix Metalloproteinases 172
3.7. Histone Acetyltransferases and Deacetylases 172
3.8. DNA Methyltransferase 1 173
3.9. DNA Polymerase . 174
3.10. Ribonucleases 174
3.11. Glyoxalase I 175
4. Curcumin Binds and Modulates PKs 175
4.1. Protein Kinases 175
4.2. Cellular Sarcoma 176
4.3. Glycogen Synthase Kinase-3ß 176
4.4. ErbB2 177
5. Curcumin Directly Binds and Modulates Protein Reductases 177
5.1. Thioredoxin Reductase 177
5.2. Aldose Reductase 178
6. Others 178
7. Curcumin Clinical Trials in Cancer 179
8. Future Perspectives 180
Acknowledgment 181
References 181
Chapter Nine: Molecular Targets of Honokiol: A Promising Phytochemical for Effective Cancer Management 190
1. Introduction 191
2. Honokiol: Structure-Activity Relationship 192
3. Anticancer Effect of Honokiol 193
3.1. Cell-Cycle Arrest 193
3.2. Apoptosis Induction 193
3.3. Antiangiogenic Effect 194
3.4. Inhibition of Migration and Invasion 194
4. Molecular Targets of Honokiol 195
4.1. Signal Transducers and Activators of Transcription 195
4.2. Nuclear Factor Kappa B 197
4.3. Beta-Catenin 197
4.4. Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin 198
4.5. Epidermal Growth Factor Receptor 199
4.6. Vascular Endothelial Growth Factor and Its Receptor 200
4.7. Hypoxia-Inducible Factors 200
4.8. Cyclooxygenases 201
5. Pharmacokinetics of Honokiol 202
6. Conclusion and Future Outlook 203
Acknowledgments 204
References 204
Chapter Ten: Effects of Tea Catechins on Cancer Signaling Pathways 210
1. Introduction 211
2. Chemistry, Bioavailability, and Biotransformation of Tea Catechins 212
2.1. Chemistry 212
2.2. Bioavailability 213
2.3. Biotransformation 214
3. Inhibition of Tumorigenesis by Tea Catechins in Animal Models and Possible Mechanisms 214
3.1. Inhibition of Tumorigenesis in the Digestive Tract 215
3.2. Inhibition of Lung Tumorigenesis 215
3.3. Inhibition of Prostate Carcinogenesis 216
3.4. Human Studies 216
4. Biochemical Activities of Tea Catechins 217
4.1. Antioxidant and Pro-oxidative Activities In Vitro and In Vivo 217
4.2. High-Affinity Binding Proteins as Targets of EGCG 219
4.3. Inhibition of Enzyme Activities 221
5. Modulating Signaling Pathways and Cell Functions 222
5.1. Inhibition of Receptor Tyrosine Kinases and Other Receptors 222
5.2. Effects on 67LR 225
5.3. Inhibition of Wnt Signaling 226
5.4. Epigenetic Mechanisms 226
5.4.1. Affecting Epigenetic DNA Methylation and Histone Modification 226
5.4.2. Effect on MicroRNA 226
5.5. Other Mechanisms 227
5.5.1. Modulating p53-Dependent Events 227
5.5.2. Binding to Lipids 227
5.5.3. Binding to Nucleic Acids 228
6. Issues in Extrapopulating Studies In Vitro to Situations In Vivo 228
7. Concluding Remarks 229
Acknowledgments 230
References 230
Author Index 238
Subject Index 268
Color Plate 274