Evidence-based Anticancer Materia Medica (eBook)

Preface 5
Contents 6
Contributors 8
Introduction 12
Chapter 1 13
An Overview of Anticancer Herbal Medicines 13
1.1 Cancer Etiology and Management Approaches 14
1.2 Diet and Cancer 15
1.3 Importance of Plant-derived Natural Products in Cancer Drug Discovery 16
1.4 Curcumin 21
1.5 Eugenol 21
1.6 Resveratrol 22
1.7 Complex Plant-derive Products and Pre-clinical Studies 26
1.8 Natural Products and Standard of Care 29
1.9 Future Prospects 30
References 31
Chapter 2 49
An Evidence-based Perspective of Arsenic Trioxide (As2O3) for Cancer Patients 49
2.1 Introduction 49
2.2 History of Arsenicals Medicinal Use and Their Metabolism 50
2.3 Mechanisms of Action of As2O3 53
2.3.1 Differentiation and Oncogenic Proteins 54
2.3.2 Apoptosis 54
2.3.2.1 Reactive Oxygen Species 55
2.3.2.2 Bcl-2 55
2.3.2.3 NF-.B 55
2.3.3 Anti-Proliferative/Cell Cycle Effects 56
2.3.4 Angiogenesis Inhibition 56
2.4 From Bedside to Bench, Then to Bedside Again 56
2.4.1 Clinical Trials in Hematologic Malignancies 57
2.4.2 Clinical Trials in Solid Tumors 60
2.5 Mechanisms of Resistance to As2O3 64
2.6 MicroRNA and As2O3 in Cancer Research 66
2.7 As2O3 and Cancer Stem Cells 67
2.8 Synergy of Arsenic with Other Agents 68
2.9 Safety and Tolerability 69
2.10 Conclusions and Future Perspectives 70
References 71
Chapter 3 77
An Evidence-based Review of Astragalus membranaceus (Astragalus) for Cancer Patients 77
3.1 Introduction 77
3.2 Applications in Traditional Medicine 78
3.3 Botany and Phytochemistry 79
3.4 Dosage and Toxicity 80
3.4.1 Dosage 80
3.4.2 Toxicity 80
3.5 In Vitro and Animal Studies 80
3.5.1 Immunomodulation 80
3.5.2 Inflammation 81
3.5.3 Antioxidant Effects 82
3.5.4 Cytostatic and Cytotoxic Effects 82
3.5.5 Hematopoiesis 83
3.6 Protective Effects on Organs and Tissues 83
3.6.1 Liver 83
3.6.2 Kidneys 84
3.6.3 Heart 84
3.6.4 Nervous System 85
3.6.5 Bone 85
3.7 Astragalus for Stress and Glycemic Control 85
3.8 Clinical Studies 86
3.9 Herb-Drug Interactions and Other Concerns 89
3.10 Future Research 89
3.11 Conclusions 90
References 90
Chapter 4 97
An Evidence-based Perspective of Panax Ginseng (Asian Ginseng) and Panax Quinquefolius (American Ginseng) as a Preventing or Supplementary Therapy for Cancer Patients 
97 
4.1 Introduction 98
4.2 Preparations of Ginseng Powders and Saponins 99
4.3 Evidences of Ginseng as a Preventing or Supplementary Therapy for Cancer 100
4.3.1 In Vitro Experimental Evidences 100
4.3.2 In Vivo Animal Test Evidences 103
4.3.3 Evidence-Based on Human Studies 104
4.4 Perspectives and Challenges 106
References 107
Chapter 5 109
Panax Quinquefolius (American Ginseng) and Panax Notoginseng (Notoginseng) in Cancer Chemoprevention 109
5.1 Introduction 109
5.2 Medicinal Use of Botanicals in Ginseng Family 110
5.3 American Ginseng 112
5.4 Notoginseng 113
5.5 Saponin Structure-activity Observation and Heat-treatment of Ginsengs 115
5.6 Perspectives and Challenges 117
References 118
Chapter 6 122
An Evidence-Based Perspective of Coptis Chinensis (Chinese Goldthread) for Cancer Patients 122
6.1 Introduction 123
6.2 Anticancer Effects of Herbal Complexes Containing Chinese Goldthread 124
6.2.1 Effect of YiQiJueDu Granule (YQJDG) on Anti-nasopharyngeal Carcinoma (NPC) 124
6.2.1.1 Inhibitory Effect of YQJDG on the Proliferation of NPC Cells 124
6.2.1.2 Inhibitory Effect of YQJDG on the Growth of Implant Tumors of NPC Cells 124
6.2.1.3 Inhibitory Effect of YQJDG on Nasopharyngeal Tumorigenesis Induced by N,N'-dinitrosopiperazine 125
6.2.1.4 Therapeutic Effect of YQJDG on Patients with Nasopharyngeal Pre-cancerous Lesions 125
6.2.1.5 Therapeutic Effect of YQJDG on Individuals at High Risk for NPC 125
6.2.1.6 YQJDG Enhance Therapeutic Effect and Reduce Toxicity of Radiationtherapy on Patients with NPC 126
6.2.2 Anti-liver Cancer Effect of San-Huang-Xie-Xin Decoction 126
6.2.3 Anticancer Effect of ZuoJin Pill 126
6.3 Anticancer Effects of the Single Herb Chinese Goldthread 127
6.4 Anticancer Effects of Chinese Goldthread Extracts 127
6.4.1 Anticancer Effects of Berberine 128
6.4.1.1 Inhibitory Effect of Berberine on the Proliferating Activity of Tumor Cells 128
6.4.1.2 Anti-angiogenic Effect of Berberine on Tumor Tissue 130
6.4.1.3 Inhibitory Effect of Berberine on the Metastatic Potential of Cancer Cells 131
6.4.1.4 Anticancer Effect of Berberine in Animal Experiments 132
6.4.1.5 Effect of Berberine on Prevention of Carcinogenesis 132
6.4.1.6 Berberine Combining with Other Antitumor Therapies to Enhance Therapeutic Effect and Reduce Toxicity 133
6.4.1.7 Potential Toxicity and Adverse Effects of Berberine 134
6.4.2 Effect of Coptisine 135
6.4.2.1 Anticancer Effect of Coptisine 135
6.4.2.2 Potential Toxicity and Adverse Effects of Coptisine 136
6.5 Perspectives and Challenges 136
References 136
Chapter 7 142
An Evidence-based Perspective of Angelica Sinensis (Chinese Angelica) for Cancer Patients 142
7.1 Angelica Sinensis (Chinese Angelica or Dong Quai) as a Traditional Chinese Medicine 143
7.2 Other Anticancer Studies on Chinese Angelica 143
7.3 Chinese Angelica on Clinical Trial of Cancer Patient 144
7.4 The Root of Chinese Angelica 145
7.5 Chloroform Extract AS-C of Chinese Angelica: Antitumor Effect In Vitro and In Vivo 146
7.5.1 The p53-Dependent Apoptosis Pathway 148
7.5.2 The Fas-FasL-Induced Apoptosis Pathway 148
7.6 BP is AS-C’s Major Antitumor Component Which Can Suppress Telomerase Activity 149
7.7 Using Oligodeoxynucleotide-based Microarray Analysis to Determine BP’s Effectors Against GBM 150
7.8 BP Causes Nur77-Translocation Leading to Tumor Apoptosis 151
7.9 BP’s Inhibition of Telomerase Activity Can Cause Tumor Senescence and Contribute to Tumor Apoptosis 152
7.10 Therapeutic Effects of the Chloroform Extract of Chinese Angelica on a Rat’s In Situ GBM Tumor 153
7.11 Therapeutic Effects of the Chloroform Extract of Chinese Angelica on Xenograft Tumor Growth 153
7.12 Cytotoxic Activity of the Chloroform Extract of Chinese Angelica on a Human GBM Tumor In Vivo 154
7.13 Antitumor Effects of BP on the Survival of Animals Bearing Subcutaneous GBM Tumors 154
7.14 Antitumor Effects of BP on the In Situ GBM Tumors of Rats 154
7.15 Autologous Implantation of RG2 into a Rat Brain as a Model for Studying the BP Antitumor Effect 155
7.16 Heterologous Implantation of Human GBM into Nude Mice as a Model to Study BP’s Antitumor Effect 155
7.17 Nur77 Is One of the Promising Effectors of BP Against Brain GBM 156
7.18 BP’s Use Against Brain GBM Mediates Tumor Senescence by Suppressing Telomerase 157
7.19 Helping BP Cross the Blood-brain Barrier 157
7.20 Conclusion and Perspectives 158
References 159
Chapter 8 165
An Evidence-based Perspective of Scutellaria Barbata (Skullcap) for Cancer Patients 165
8.1 Introduction 166
8.2 Early Studies 166
8.2.1 Anti-mutagenesis and Anti-carcinogenesis Chemo-prevention Properties 166
8.2.2 Immune Enhancing and Anti-inflammation Effect of Skullcap 167
8.3 Chemical Constitution 167
8.4 Anticancer In Vitro and In Vivo Animal Studies 178
8.4.1 In Vitro Murine Cancer Cell Line Studies 178
8.4.2 In Vivo Murine Models 178
8.5 Anticancer In Vitro Human Cell Lines and Clinical Studies 179
8.5.1 In Vitro Cell Line Studies 179
8.5.2 Clinical Studies 180
8.6 Discussion 181
8.6.1 Prospective Therapeutic Application and Direction for Cancer Patients 181
8.6.1.1 Breast Cancer 181
8.6.1.2 Prostate Cancer 182
8.6.1.3 Liver, Colorectal, Uterine, and Lung Cancers 182
8.6.2 Prospective and Challenges 183
References 184
Chapter 9 188
An Evidence-based Perspective of Hedyotis Diffusa or Oldenlandia Diffusa (Spreading Hedyotis) for Cancer Patients 188
9.1 Introduction 188
9.2 Pre-clinical Studies 189
9.2.1 Chemical Components 189
9.2.2 In Vitro and in Vivo Anticancer Effects and Mechanisms 190
9.2.2.1 Anticancer Effects 190
9.2.2.2 Immune Modulation 193
9.2.3 Toxicity and Side Effects 194
9.3 Clinical Studies and Applications 194
9.3.1 Esophagus Cancer 195
9.3.2 Leukemia 195
9.3.3 Non-small Cell Lung Cancer 195
9.3.4 Liver Cancer 196
9.3.5 Various Cancers 197
9.3.6 Clinical Applications and Representative Formulas 198
9.3.7 Dosage Forms and Doses 198
9.4 Concluding Remarks and Perspectives 199
References 199
Chapter 10 202
An Evidence-based Perspective of Allium Sativum (Garlic) for Cancer Patients 202
10.1 Introduction 202
10.2 Bioactive Compounds Derived from Garlic 203
10.3 Human Studies 205
10.4 Evidence of the Anticancer Activity of Garlic in Animal Models 210
10.5 Molecular Targets of Garlic Compounds—In Vitro Studies 215
10.6 Antioxidant and Pro-oxidant Activity of Garlic and OSCs 221
10.7 Adverse Effects of Garlic and Its Interactions with Drugs 222
10.8 Other Therapeutic Applications 223
10.9 Summary and Conclusions 224
References 225
Chapter 11 233
An Evidence-based Perspective of Curcuma Longa (Turmeric) for Cancer Patients 233
11.1 The Plant and Its History 234
11.2 Activities and Mechanism of Curcumin as an Anticancer Agent 235
11.3 Clinical Studies with Curcumin 241
11.4 Cancer Prevention 241
11.5 Pancreatic Cancer 243
11.6 Colorectal Cancer 244
11.7 Breast Cancer 245
11.8 Other Cancers and Ongoing Studies 246
11.9 Toxicity 246
11.10 Conclusion 247
References 248
Chapter 12 252
An Evidence-based Perspective of Ganoderma Lucidum (Lucid Ganoderma) for Cancer Patients 252
12.1 Introduction 253
12.2 Clinical Trials of Cancer Patients 253
12.3 Anticancer Activity of Lucid Ganoderma and Its Crude Extracts 255
12.4 Active Components with Anticancer Activity in Lucid Ganoderma 257
12.4.1 Triterpenoids and Steroids 257
12.4.2 Polysaccharides 258
12.4.3 Other Active Compounds 258
12.5 Anticancer Mechanisms for Lucid Ganoderma 259
12.5.1 Cell Cycle Arrest 259
12.5.2 Apoptosis 260
12.5.3 Anti-invasion and Anti-migration 260
12.5.4 Anti-angiogenesis 261
12.5.5 Immunomodulation 262
12.5.6 Others 263
12.6 Anticancer Activity of Combination Treatment 263
12.7 Safety of Lucid Ganoderma in Clinical Trials 264
12.8 Conclusion 265
References 265
Chapter 13 271
An Evidence-based Perspective of Coriolus Versicolor (Multicolored Polypore Mushroom) for Cancer Patients 271
13.1 Traditional and Contemporary Uses 272
13.2 Active Constituents and Products 273
13.2.1 Polysaccharides and Glyco-conjugates 275
13.2.1.1 ß-D-glucans 275
13.2.1.2 Heteropolysaccharides 275
13.2.1.3 Dietary Fibers 275
13.2.1.4 Glyco-conjugates 276
13.2.2 Terpenes 276
13.2.3 Phenolic Compounds 277
13.2.4 Other Active Low Molecular Weight Compounds 277
13.2.4.1 Active Hexose Correlated Compound (AHCC) 277
13.2.4.2 Lipid Compounds 277
13.2.4.3 Vitamins 278
13.2.4.4 Mineral and Trace Elements and Other Low Molecular Weight Compounds 278
13.3 Pharmacological Actions of the Active Ingredients 278
13.3.1 Effects on Hematopoietic Stem Cells 278
13.3.2 Effects on Immune System 279
13.3.2.1 Recognition and Receptors 279
13.3.2.2 Effects of on the Innate Immune System 281
13.3.2.3 Effects on Adaptive Immunity 283
13.3.2.4 Effects on Cytokine Production 285
13.3.3 Direct Antitumor Effects, Molecular Targets and Signaling Pathways Affected by the Compounds 285
13.3.4 Other Pharmacological Effects 287
13.3.4.1 Antimicrobial Effects 287
13.3.4.2 Hepatoprotective and Analgesic Effect 288
13.4 Clinical and Experimental Evidence for Anticancer Properties 288
13.4.1 Animal Studies 288
13.4.2 Clinical Studies 290
13.4.2.1 PSP Trials 290
13.4.2.2 PSK Trials 291
13.5 Safety Studies 298
13.6 Translating the Pharmacologic Potential of Multicolored Polypore Mushroom into an Anticancer Agent 299
13.7 Concluding Remarks 300
References 301
Chapter 14 309
An Evidence-based Perspective of Lentinus Edodes (Shiitake Mushroom) for Cancer Patients 309
14.1 Introduction 309
14.2 Testing Antitumor Activity in Animals 312
14.3 Epidemiological Data from Clinical Studies 313
14.4 Determination of Optimal Dosage and Administration Timing 314
14.4.1 Mechanisms of Antitumor and Immunomodulating Action by Lentinan (Fig. 14.1) 315
14.4.2 Molecular Mechanism by Which Shiitake Mushroom Affects Immunity Response 316
14.5 Prospective Use in Clinical Therapy and Drug-lentinan Interaction 316
14.6 Toxicity and Adverse Effects 318
References 319
Chapter 15 324
Molecular Targets of Resveratrol in Carcinogenesis 324
15.1 Introduction 324
15.2 Regulation of Phase I and Phase II Xenobiotic Metabolizing Enzymes 326
15.2.1 Cytochrome P450 (CYP) Enzymes 332
15.2.2 Nrf2 332
15.3 Modulation of Cell Cycle Progression and Apoptosis 333
15.3.1 Cell Cycle Proteins 333
15.3.2 Apoptosis 335
15.4 Suppression of the Inflammatory Signaling Pathway 335
15.4.1 COX-2 336
15.4.2 Pro-inflammatory Cytokines: TNF-a and ILs 336
15.5 Inhibition of Angiogenesis, Invasion, and Metastasis 337
15.5.1 HIF-1a and VEGF 337
15.5.2 MMP2 and MMP9 337
15.6 Effect as a Selective Estrogen Receptor Modulator 338
15.7 Other Molecular Targets 339
15.7.1 Topoisomerase II 339
15.7.2 Human Telomerase Reverse Transcriptase (hTERT) 339
15.8 Identification of Novel Molecular Targets 340
15.8.1 ATF3 (Activating Transcription Factor 3) 341
15.8.2 NAG-1(Non-steroidal Anti-inflammatory Drug-activated Gene-1) 341
15.8.3 DDIT3 (DNA-Damage-Inducible Transcript 3) 342
15.8.4 Other Potential Targets 342
15.9 Conclusion 343
References 344
Chapter 16 353
An Evidence-based Perspective of Camellia Sinensis (Green Tea) for Cancer Patients 353
16.1 Introduction 354
16.2 Evidence of Cancer Prevention from Animal Studies 355
16.2.1 Green Tea and GTP 356
16.2.2 Caffeine 357
16.2.3 Effects on In Vivo Antioxidants and Carcinogen Metabolism 358
16.2.4 Green Tea in Combination with Other Compounds 359
16.3 Evidence of Cancer Prevention from Human Studies 361
16.3.1 Epidemiological Studies 361
16.3.1.1 Lung Cancer 362
16.3.1.2 Breast Cancer 362
16.3.1.3 Prostate Cancer 363
16.3.1.4 Esophageal, Stomach, and Colon Cancer 364
16.3.2 Human Intervention Studies 365
16.4 Protection against Chemotherapy Side-effects 367
16.5 Potential Toxicity of High-dose Oral GTP 367
16.6 Conclusions and Future Directions 369
References 371
Chapter 17 378
Mylabris Phalerata (Chinese Blister Beetle) on Hematological Malignancies 378
17.1 Introduction 379
17.2 Cantharidin (CTD) 379
17.3 Effects of CTD on Tumor Cells 380
17.3.1 Protein Phosphatase Activity 380
17.3.2 Microarray Analysis 381
17.3.3 DNA Damage and Repair Induced by CTD 383
17.4 Effects of CTD on Malignant Hematological Cells 383
17.4.1 Therapeutic Approaches to the Treatment of Leukemia 383
17.4.2 Effects of CTD on Leukemia 385
17.4.3 Therapeutic Approaches to Multiple Myeloma 386
17.4.4 Effects of CTD on Myeloma Cells 387
17.5 Conclusion 387
References 388
Chapter 18 392
An Evidence-based Perspective of Bufo Gargarizans (Asiatic Toad) for Cancer Patients 392
18.1 Introduction 393
18.2 Natural Sources 394
18.3 Chemical Structures 395
18.4 Traditional Functions 395
18.5 Effects on Steroidogenesis 396
18.5.1 Testosterone 396
18.5.2 Progesterone, Glucocorticoid, and Mineralocorticoid 397
18.6 Anticancer Effects and Cancer Therapy 397
18.6.1 Leukemia 397
18.6.1.1 Differentiation Inducing Agent 398
18.6.1.2 Na+,K+-ATPase Inhibitor 398
18.6.1.3 Topoisomerase II Inhibitor 398
18.6.1.4 Apoptosis Inducing Agent 399
18.6.2 Prostate Cancer 399
18.6.3 Gynaecological Cancer 400
18.6.4 Lung Cancer 400
18.6.5 Hepatocellular Carcinoma 401
18.6.5.1 In Vitro Study 401
18.6.5.2 In Vivo Study 401
18.6.5.3 Clinical Study 402
18.6.6 Gallbladder Carcinoma 402
18.6.7 Other Cancer Types 403
18.6.7.1 Gastric Cancer 403
18.6.7.2 Osteosarcoma 403
18.6.7.3 Pancreatic Cancer 404
18.7 Herb-drug Interaction, Toxicity, and Adverse Effects 405
18.8 Perspectives 405
References 406
Chapter 19 411
An Evidence-based Perspective of Herbal Remedies for Cancer Patients 411
19.1 Introduction 412
19.1.1 Defining a “Herbal Medicine” and a “Herbal Remedy” 412
19.1.2 Role of Herbal Remedies in Cancer Prevention and Treatment 412
19.2 Herbal Medicines and Their Primary Modes of Action 413
19.2.1 Inducing Apoptosis 413
19.2.2 Inhibiting Angiogenesis 414
19.2.3 Overcoming Multi-drug Resistance (MDR) 415
19.2.4 Boosting the Immune System 416
19.3 Experimental Perspectives of Effective Herbal Ingredients in Cancer Therapy 416
19.3.1 Alkaloids 416
19.3.1.1 Berberine 416
19.3.1.2 Camptothecin and Its Analogues 417
19.3.1.3 Matrine 418
19.3.2 Flavonoids 418
19.3.3 Glycosides 419
19.3.4 Polysaccharides 419
19.3.5 Miscellaneous 419
19.4 Clinical Perspectives of Herbal Remedies in Combination Cancer Therapy 420
19.4.1 Lung Cancer 420
19.4.2 Breast Cancer 421
19.4.3 Colorectal Cancer 422
19.4.4 Gastric Cancer 423
19.4.5 Esophageal Cancer 423
19.4.6 Prostate Cancer 424
19.4.7 Liver Cancer 424
19.4.8 Leukemia 425
19.4.9 Nasopharyngeal Carcinoma (NPC) 425
19.5 Herbal Remedies in Terminal/Palliative Cancer Care 426
19.6 Future Prospects 426
19.6.1 The Road Ahead for Herbal Remedies—New Strategies in the Fight Against Cancer 426
19.6.2 Clinical Acceptance of Herbal Remedies—“Evidence” is the Key to Success 427
References 428
Index 435