Developmental therapeutics: Review of biologically based complementary and alternative medicine (CAM) therapies for potential application in children with cancer-part II

Journal of Pediatric Hematology/Oncology

Volumn 28, Issue 5, 2006, Pages 271-285

  Melnick, Steven J ^a  

^a MIAMI CHILDREN'S HOSPITAL   (United States)

Author keywords

Biologically based CAM therapies; Cancer; Children; Developmental therapeutics

Indexed keywords

ABNOBA; ALKALOID; ALPHA TOCOPHEROL; ANTINEOPLASTIC AGENT; ANTIOXIDANT; ASCORBIC ACID; CAFFEIC ACID; CATECHIN; CURCUMIN; CYCLOOXYGENASE 2; ELLAGIC ACID; ERLOTINIB; GINSENG EXTRACT; GINSENOSIDE; GREEN TEA EXTRACT; KRESTIN; LUTEOLIN; POLYPHENOL DERIVATIVE; PROTEIN C JUN; RETINOL; RUTOSIDE; SELENIUM; VISCUM ALBUM EXTRACT; VISCUM ALBUM LECTIN;

ALTERNATIVE MEDICINE; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; AYURVEDA; BLADDER CANCER; BREAST CANCER; CAMILLIA SINENSIS; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INCIDENCE; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER THERAPY; CARCINOGENESIS; CHILDHOOD CANCER; CHINESE MEDICINE; CLINICAL TRIAL; COCHRANE LIBRARY; COLON CANCER; CURCUMA LONGA; DATA BASE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SOLUBILITY; DRUG TOLERABILITY; EMBASE; ENZYME INHIBITION; EVIDENCE BASED MEDICINE; GANODERMA LUCIDUM; GENE EXPRESSION; GINGER; GINSENG; HUMAN; IMMUNOMODULATION; IN VIVO STUDY; KIDNEY CANCER; LENTINUS EDODES; LEUKEMIA; LIVER CANCER; LUNG CANCER; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; MEDICINAL PLANT; MEDLINE; MELANOMA; MUSHROOM; NONHUMAN; ONCOGENE C FOS; ONCOGENE C MYC; OREGANO; OVARY CANCER; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PALLIATIVE THERAPY; PERICARP; POMEGRANATE; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; ROSEMARY; SCUTELLARIA; STATISTICAL SIGNIFICANCE; STRUCTURE ACTIVITY RELATION; TEA; TRADITIONAL MEDICINE; VISCUM ALBUM;

CHILD; COMPLEMENTARY THERAPIES; HUMANS; MICRONUTRIENTS; NEOPLASMS; PLANTS, MEDICINAL; RANDOMIZED CONTROLLED TRIALS;

EID: 33745256474     PISSN: 10774114     EISSN: 15363678     Source Type: Journal    
DOI: 10.1097/01.mph.0000212900.76523.16     Document Type: Review

References (233)

1. Cooper EL. Commentary on traditional and modern biomedical prospecting. Part II: The benefits. Evidenced-Based Complementary and Alternative Medicine. 2004;1:207-209.
2. Zakrzewski PA. Bioprospecting or biopiracy? the pharmaceutical industry's use of indigenous medicinal plants as a source of potential drug candidates. Univ Toronto Med J. 2002;79:252-254.
3. Institute of Medicine of the National Academies. Complementary and Alternative Medicine in the United States. Washington, DC: The National Academic Press; 2005.
4. National Center for Complementary and Alternative Medicine. Biologically Based Practices: An Overview. Available at: http://nccam.nih.gov/health/ backgrounds/biobasedprac.htm. Accessed July 3, 2005.
5. National Centre for Agri-Food Research in Medicine. An Introduction to Functional Foods, Nutraceuticals and Natural Health Products. Available at: http://www.sbrc.ca/ncarm/intro-funcfoods.htm. Accessed July 3, 2005.
6. Ernst E. Prevalence of the use of complementary/alternative medicine: A systematic review. Bull World Health Organ. 2000;78:252-257.
7. Friedman T, Slayton WB, Allen LS, et al. Use of alternative therapies for children with cancer. Pediatrics. 1997;100:1-6.
8. Barnes PA, Powell-Griner E. Complementary and alternative medicine use among adults: United States, 2002. Advance Data, Centers for Disease Control. 2004;343:1-20.
9. Wargovich MJ, Woods C, Hollis DM, et al. Herbals, cancer prevention and health. J Nutr. 2001;131:3034S-3036S.
10. Citrin DL, Gupta D, Birdsall TC, et al. Prevalence of use of herbal therapies in adult cancer patients: Potential for herb-drug interactions. ASCO Meeting Abstracts 2005;23:6086.
11. Richardson MA, Sanders T, Palmer JL, et al. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18:2505-2514.
12. Mans DRA, Da Rocha AB, Schwartsmann G. Anti-cancer drug discovery and development in brazil: Targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds. The Oncologist. 2000;5:185-198.
13. Firn RD. Bioprospecting: Why is it so unrewarding? Biodiversity Conservation. 2003;12:207-216.
14. Müller WEG, Batel R, Schröder HC, et al. Traditional and modern biomedical prospecting. Part I: The history. Evidenced-Based Complementary and Alternative Medicine. 2004;1:71-82.
15. Müller WEG, Schröder HC, Wiens M, et al. Traditional and modern biomedical prospecting. Part II: The benefits. Evidenced-Based Complementary and Alternative Medicine. 2004;1:133-144.
16. Theis N, Lerdau M. The evolution of function in plant secondary metabolites. Int J Plant Sci. 2003;164:S93-S102.
17. Sporn MB, Suh N. Chemoprevention of cancer. Carcinogenesis. 2000;21:525-530.
18. Trapp SC, Croteau RB. Genomic organization of plant terpene synthases and molecular evolutionary implications. Genetics. 2001;158:811-832.
19. Ourisson G. The general role of terpenes and their global significance. Pure Appl Chem. 1990;62:1401-1404.
20. Cox PA, Balick MJ. The ethnobotanical approach to drug discovery. Sci Am. 1994;270:82-87.
21. Briskin DP. Medicinal plants and phytomedicines: Linking plant biochemistry and physiology to human health. Plant Physiol. 2000;124:507-514.
22. Tyler VE. Phytomedicines: Back to the future. J Nat Prod. 1999;62:1589-1592.
23. Hankey A. Ayurvedic physiology and etiology: Ayurvedo amritanaam. The doshas and their functioning in terms of contemporary biology and physical chemistry. J Altern Complement Med. 2001;7:567-574.
24. Subbarayappa BV. The roots of ancient medicine: An historical outline. J Biosci. 2001;26:135-144.
25. Gerson S. Ayurvedic medicine antitoxification versus detoxification. Altern Complement Ther. 2001;7:233-239.
26. Hankey A. The scientific value of ayurveda. J Altern Complement Med. 2005;11:221-225.
27. Hankey A. CAM modalities can stimulate advances in theoretical biology. Evidenced-Based Complementary and Alternative Medicine. 2005;2:5-12.
28. Singh RH. An assessment of the Ayurvedic concept of cancer and a new paradigm of anticancer treatment in ayurveda. J Altern Complement Med. 2002;8:609-614.
29. Kahn S, Balick MJ. Therapeutic plants of ayurveda: a review of selected clinical and other studies for 166 species. J Altern Complement Med. 2001;5:405-515.
30. Wicke RW, Cheung CS. Principles for applying traditional Chinese medicine to cases of cancer. Integr Cancer Therapies. 2002;1:175-178.
31. Lu A-P, Jai H-W, Xiao C, et al. Theory of traditional Chinese medicine and therapeutic method of diseases. World J Gastroenerol. 2004;10:1854-1856.
32. Tan S, Tillisch K, Mayer E. Functional somatic syndromes: Emerging biomedical models and traditional Chinese medicine. Evidenced-Based Complementary and Alternative Medicine. 2004;1:35-40.
33. Horowitz S. Nutrigenomics and nutrigenics. Alternative and Complementary Therapies. 2005;11:115-120.
34. Yi Y-D, Chang I-M. An overview of traditional Chinese herbal formulas and a proposal of a new code system for expressing the formula titles. Evidenced-Based Complementary and Alternative Medicine. 2004;1:125-132.
35. Tang J-L, Zhan S-Y, Ernst E. Review of randomized controlled trials of Chinese medicine. BMJ. 1999;319:160-161.
36. Chang R, White JD. Asian therapies for cancer-coming of age. J Altern Complement Med. 2002;8:541-543.
37. Newmark TM, Schulick P. Beyond Aspirin. Prescott, AZ: Hohm Press; 2000.
38. Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res. 2000;33:179-189.
39. Seth SD, Sharma B. Medicinal plants in India. Indian J Med Res. 2004;120:9-11.
40. Harkey MR, Henderson GL, Gershwin ME, et al. Variability in commercial ginseng products: An analysis of 25 preparations. Am J Clin Nutr. 2001;73:1101-1106.
41. Patocka J. Biologically active pentacyclic triterpenes and their current medicine signification. J Appl Biomed. 2003;1:7-12.
42. Thurnher D, Turhani D, Pelzmann M, et al. Betulinic acid: A new cytotoxic compound against malignant head and neck cancer cells. Head Neck. 2003;25:732-740.
43. Tan Y, Yu R, Pezzuto JM. Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation. Clin Cancer Res. 2003;9:2866-2875.
44. Hata K, Hori K, Ogasawara H, et al. Anti-leukemia activities of Lup-28-al-20(29)-en-3-one, a lupine triterpene. Toxicol Letters. 2003;143:1-7.
45. Chaterjee P, Kouzi SA, Pezzuto JM, et al. Biotransformation of the antimelanoma agent betulinic acid by bacillus megaterium ATCC 13368. Appl Environ Microbiol. 2000;66:3850-3855.
46. Schmidt ML, Kuzmanoff KL, Ling-Indeck L, et al. Betulinic acid induces apoptosis in human neuroblastoma cell lines. Eur J Cancer. 1997;33:2007-2010.
47. Syrovets T, Buchele B, Gedig E, et al. Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIα. MOL. 2000;58:71-81.
48. Shao Y, Ho CT, Chin CK, et al. Inhibitory activity of boswellic acids from Boswellia serrata against human leukemia HL-60 cells in culture. Planta Med. 1998;64:328-331.
49. Syrovets T, Gschwend JE, Büchele B, et al. Inhibition of IκB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. J Biol Chem. 2005;280:6170-6180.
50. Liu J-J, Nilsson A, Oredsson S, et al. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis. 2002;23:2087-2093.
51. Winking M, Sarikaya S, Rahmanian A, et al. Boswellic acids inhibit glioma growth: A new treatment option? J Neurooncol. 2000;46:97-103.
52. Janssen G, Bode U, Breu H, et al. Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Klin Padiatr. 2000;212:189-195.
53. Ju YH, Clausen LM, Allred KF, et al. β-sitosterol, β-sitosterol glucoside, and a mixture of β-sitosterol and β-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells In vitro and in ovariectomized athymic mice. J Nutr. 2004;134:1145-1151.
54. Choi YH, Kong KR, Kim YA, et al. Induction of bax and activation of caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells. Int J Oncol. 2003;23:1657-1662.
55. Popovich DG, Kitts DD. Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch Biochem Biophys. 2002;406:1-8.
56. 1 cells in two cultured intestinal cell lines, Int-407 and Caco-2. Can J Physiol Pharmacol/Rev Can Physiol Pharmacol. 2004;82:183-190.
57. Chang YS, Seo E-K, Gyllenhaal C, et al. Panax ginseng: A role in cancer therapy? Integr Cancer Ther. 2003;2:13-33.
58. Rao CV, Newmark HL, Reddy BS. Chemopreventive effect of squalene on colon cancer. Carcinogenesis. 1998;19:287-290.
59. Harmand PO, Duval R, Liagere B, et al. Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells. Int J Oncol. 2003;23:105-112.
60. Subbaramaiah K, Michaluart P, Sporn MB, et al. Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Cancer Res. 2000;60:2399-2404.
61. Shishodia S, Majumdar S, Banerjee S, et al. Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation: Correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and Cyclin D1. Cancer Res. 2003;63:4375-4383.
62. Li J, Guo W-J, Yang Q-Y. Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15. World J Gastroenterol. 2002;8:493-495.
63. Mujoo K, Haridas V, Hoffmann JJ, et al. Triterpenoid saponins from Acacia victoriae (Bentham) decrease tumor cell proliferation and induce apoptosis. Cancer Res. 2001;61:5486-5490.
64. Haridas V, Higuchi M, Jayatilake GS, et al. Avicins: Triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation. PNAS. 2001;98:5821-5826.
65. Hanausek M, Ganesh P, Walaszek Z, et al. Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), suppress H-ras mutations and aneuploidy in a murine skin carcinogenesis. PNAS. 2001;98:11551-11556.
66. Hsu M-J, Cheng J-S, Huang H-C. Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c-myc, p53, and bcl-2 mRNA. Br J Pharmacol. 2000;131:1285-1293.
67. Ramachandran C, Rabi T, Fonseca HB, et al. Novel plant triterpenoid drug amooranin overcomes multidrug resistance in human leukemia and colon carcinoma cell lines. Int J Cancer. 2003;105:784-789.
68. Rabi T, Ramachandran C, Fonseca HB, et al. Novel drug amooranin induces apoptosis through caspase activity in human breast carcinoma cell lines. Breast Cancer Res Treat. 2003;80:321-330.
69. Ikeda T, Nakata Y, Kimura F, et al. Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3, 12-dioxoolean-1,9-dien-28-oic acid. Mol Cancer Ther. 2004;3:39-45.
70. Stadheim TA, Suh N, Ganju N, et al. The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) potently enhances apoptosis induced by tumor necrosis factor in human leukemia cells. J Biol Chem. 2002;277:16448-16455.
71. Ikeda T, Sporn M, Honda T, et al. The novel triterpenoid CDDO and its derivatives induce apoptosis by disruption of intracellular redox balance. Cancer Res. 2003;63:5551-5558.
72. Ito Y, Pandey P, Sporn MB, et al. The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol. 2001;59:1094-1099.
73. Place AE, Suh N, Williams CR, et al. The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo. Clin Cancer Res. 2003;9:2798-2806.
74. Konopleva M, Tsao T, Ruvolo P, et al. Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia. Blood. 2002;99:326-335.
75. Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000;130:2073S-2085S.
76. Youdim KA, Spencer JPE, Schroeter H, et al. Dietary flaveonoids as potential neuroprotectants. Biol Chem. 2002;383:503-519.
77. Koo JL, Min DB. Reactive oxygen species, aging, and antioxidative nutraceuticals. Comprehens Rev Food Sci Food Safety. 2004;3:21-33.
78. Finley JW. Proposed criteria for assessing the efficacy of cancer reduction by plant foods enriched carotenoids, glucosinolates, polyphenols and selenocompounds. Ann Botany. 2005;95:1075-1096.
79. Urauiaga I, Leighton F. Plant polyphenol antioxidants and oxidative stress. Biol Res. 2000;33:55-64.
80. Ross JA, Kaufmann CM. Dietary flavonoids: bioavailability, metabolic effects and safety. Ann Rev Nutr. 2002;22:19-34.
81. Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in food: their role in the prevention of cardiovascular disease and cancer. Am J Med. 2002;113(Suppl 9B):71S-88S.
82. Cronin JR. Curcumin. Alternative and Complementary Therapies. 2003;9:34-38.
83. Ramachandran C, Rodriguez S, Ramachandran R, et al. Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005;25: in press.
84. Tripathy YB, Tripathy P, Arjmani BH. Nutraceuticals and cancer management. Frontiers Biosci. 2005;10:1607-1618.
85. Brouet I, Ohshima H. Curcumin, an anti-tumor promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun. 1995;206:533-540.
86. Korutla L, Kumar R. Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta. 1994;1224:597-600.
87. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995;270:24995-25000.
88. Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta. 1994;1224:255-263.
89. Shao Z-M, Shen Z-Z, Liu C-H, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int J Cancer. 2002;98:234-240.
90. Gururaj AE, Belakavadi M, Venkatesh DA. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Commun. 2002;297:934-942.
91. Lu YP, Chang RL, Lou YR, et al. Effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate- and ultraviolet B light-induced expression of c-Jun and c-Fos in JB6 cells and in mouse epidermis. Carcinogenesis. 1994;15:2363-2370.
92. Kakar SS, Roy D. Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin. Cancer Lett. 1994;87:85-89.
93. Ramachandran C, Fonseca HB, Jhabvala P, et al. Curcumin inhibits telomerase activity through human telomerase reverse transcriptase in MCF-7 breast cancer cell line. Cancer Lett. 2002;184:1-6.
94. Ramachandran C, You W. Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Res Treat. 1999;54:269-278.
95. Karunagaran D, Rashmi R, Kumar TR. Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer Drug Targets. 2005;5:117-129.
96. Reed JC. Apoptosis-based therapies. Nat Rev Drug Discov. 2002;1:111-121.
97. Lee J, Im Y-H, Jung HH, et al. Curcumin inhibits interferon-α induced NF-κB and COX-2 in human A549 non-small cell lung cancer. Biochem Biophys Res Commun. 2005;334:313-318.
98. Lev-Ari S, Maimon Y. Down regulation of PGE2by curcumin is correlated with inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines. Abstr. 81. Society for Integrative Oncology, 1st International Conference. 2004:64.
99. Tang X-G, Bi H, Feng J-G, et al. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacologica Sinica. 2005;8:1009-1016.
100. Limtrakul P, Anuchapreeda S, Buddhasukh D. Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids. BMC Cancer. 2004;4:13-18.
101. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895-2900.
102. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7:1894-1900.
103. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: Biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10:6847-6854.
104. Mansky PJ, Grem J, Wallerstedt DB, et al. Mistletoe and gemcitabine in patients with advanced cancer: A model for the phase I study of botanicals and botanical-drug interactions in cancer therapy. Integrat Cancer Ther. 2003;2:345-352.
105. Kaegi E. Unconventional therapies for cancer: 3. Iscador. CMAJ. 1998;158:1157-1159.
106. National Cancer Institute. Mistletoe (PDQ®) [Cancer information summary]. Available at: http://www.cancer.gov/cancertopics/pdq/cam/mistletoe/ healthprofessional. Accessed August 1, 2005.
107. Giudici M, Pascual R, de la Canal L, et al. Interaction of viscotoxins A3 and B with membrane model systems: Implications to their mechanism of action. Biophys J. 2003;85:971-981.
108. Van Huyen J-PD, Bayry J, Delignat S, et al. Induction of apoptosis of endothelial cells by Viscum album: A role for anti-tumoral properties of mistletoe lectins. Mol Med. 2002;8:600-606.
109. Urech K, Scher M, Hostanska K, et al. Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L. JPP. 2005;57:101-109.
110. Jung MJ, Yoo YC, Lee KB, et al. Isolation of epi-oleanolic acid from Korean mistletoe and its apoptosis-inducing activity in tumor cells. Arch Pharm Res. 2004;27:840-844.
111. Rios MY, Salina D, Villarreal ML. Cytotoxic activity of moronic acid and identification of the new triterpene 3,4-seco-olean-18-ene-3,28-dioic acid from Phoradendron reichenbachianum. Planta Med. 2001;67:443-446.
112. Bantel H, Engels IH, Klaus Schulze-Osthoff WV, et al. Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res. 1999;59:2083-2090.
113. Hajtó T, Hostanska K, Berki T, et al. Oncopharmacological perspectives of a plant lectin (Viscum album agglutinin-I): Overview of recent results from in vitro experiments and in vivo animal models, and their possible relevance for clinical applications. Evidenced-Based Complementary and Alternative Medicine. 2005;2:59-67.
114. Kourmanova AG, Soudarkinal OJ, Olsnes S, et al. Cloning and characterization of the genes encoding toxic lectins in mistletoe (Viscum album L). Eur J Biochem. 2004;271:2350-2360.
115. Boneberg E-M, Hartung T. Mistletoe lectin-1 increases tumor necrosis factor-α release in lipopolysaccharide-stimulated whole blood via inhibition of interleukin-10 production. JPET. 2001;298:996-1000.
116. Moon S-H, Heo J-C, Fine RL, et al. BRD-glucan exhibits potent immunochemotherapeutic activity in vitro and in vivo. Int J Oncol. 2005;26:395-404.
117. Yan J, Vetvicka V, Xia Y, et al. β-Glucan, a "specific" biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol. 1999;163:3045-3052.
118. Nair PKR, Rodriguez S, Ramachandran R, et al. Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia. Int Immunopharmacol. 2004;4:1645-1659.
119. Boon H, Wong J. Botanical medicine and cancer: A review of the safety and efficacy. Expert Opin Pharmacother. 2004;5:2485-2501.
120. Keinle GS, Berrino F, Bussing A, et al. Mistletoe in cancer: A systematic review on controlled clinical trials. Eur J Med Res. 2003;8:109-119.
121. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: A randomised controlled clinical trial. Eur J Cancer. 2001;37:23-31.
122. Stauder H, Kreuser ED. Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: Current state of clinical research. Onkologie. 2002;25:374-380.
123. Kleeberg UR, Suciu S, Bröcker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness > 3 mm) or regional lymph node metastasis. Eur J Cancer. 2004;40:390-402.
124. Grossarth-Maticek R, Kiene H, Baumgartner SM, et al. Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: Prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med. 2001;7:57-66, 68-72, 74-76 passim.
125. Kimmel Cancer Center, National Cancer Institute. Phase II trial to study the effectiveness of mistletoe in treating patients who are receiving palliative chemotherapy for stage IIIB or stage IV non-small cell lung cancer. Available at: http://www.clinicaltrials.gov/ct/show/NCT00052325. Accessed on August 3, 2005.
126. Cooper R, Morré DJ, Morré DM. Medicinal benefits of green tea: Part I. Review of noncancer health benefits. J Altern Complement Med. 2005;11:521-528.
127. Nihal A, Hasan M. Green tea polyphenols and cancer: Biologic mechanisms and practical implications. Nutr Rev. 1999;57:78-83.
128. Mukhtar H, Ahmad N. Tea polyphenols: Prevention of cancer and optimizing health. Am J Clin Nutr. 2000;71(Suppl):1698S-1702S.
129. Miller AL. Antioxidant flavonoids: Structure, function and clinical usage. Alt Med Rev. 1996;1:103-111.
130. Amic D, Davidovic-Amic D, Beslo D, et al. Structure-radical scavenging activity relationships of flavonoids. Croatica Chemica Acta. 2003;76:55-61.
131. Brown MD. Green tea (Camellia sinensis) extract and its possible role in the prevention of cancer. Altern Med Rev. 1999;4:360-370.
132. Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: Evidence from animal studies. J. Nutr. 2003;133:3275S-3284S.
133. Sugihara N, Ohnishi M, Imamura M, et al. Differences in antioxidative efficiency of catechins in various metal-induced lipid peroxidations in cultured hepatocytes. J Health Sci. 2001;47:99-106.
134. Sugihara N, Arakawa T, Ohnishi M, et al. Anti- and pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid. Free Radic Biol Med. 1999;27:1313-1323.
135. Yang CS, Landau JM. Effects of tea consumption on nutrition and health. J Nutr. 2000;130:2409-2412.
136. Deguchi H, Fuhii T, Nakagawa S, et al. Analysis of cell growth inhibitory effects of catechin through MAPK in human breast cancer cell line T47D. Int J Oncol. 2002;21:1301-1305.
137. Leone M, Zhai D, Sareth S, et al. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic bcl-2-family proteins. Cancer Res. 2003;63:8118-8121.
138. Benelli R, Venè R, Bisacchi D, et al. Anti-invasive effects of green tea polyphenol epigallocatechin-3-Gallate (EGCG), a natural inhibitor of metallo and serine proteases. Biol Chem. 2002;383:101-105.
139. Dulak J. Nutraceuticals as anti-angiogenic agents: Hopes and reality. J Physiol Pharmacol. 2005;56(Suppl. 1):51-69.
140. Adhami VM, Ahmad N, Mukhtar H. Molecular targets for green tea in prostate cancer prevention. J Nutr. 2003;133:2417S-2424S.
141. Hubner LG. Green tea catechins and L-theanine in integrative cancer care. Altern Complement Ther. 2003;9:294-298.
142. Chung JY, Huang C, Meng X, et al. Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in h-ras-transformed cells: Structure-activity relationship and mechanisms involved. Cancer Res. 1999;59:4610-4617.
143. Yarnell E, Abascal K. Can botanicals reduce multidrug resistance in cancer? Altern Complement Med. 2002;8:336-340.
144. Van Amelsvoort JM, Van Hof KH, Mathot JN, et al. Plasma concentrations of individual tea catechins after a single oral dose in humans. Xenobiotica. 2001;31:891-901.
145. Chow H-HS, Cai Y, Alberts DS, et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev. 2001;10:53-58.
146. Lee M-J, Maliakal P, Chen L, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: Formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev. 2002;11:1025-1032.
147. Kroon PA, Clifford MN, Crozier A, et al. How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr. 2004;80:15-21.
148. Rietveld A, Wiseman S. Antioxidant effects of tea: evidence from human clinical trials. J Nutr. 2003;133:3285S-3292S.
149. Seely D, Mills EJ, Wu P, et al. The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2005;4:144-156.
150. Pisters KMW, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol. 2001;19:1830-1838.
151. National Cancer Institute. Phase II Randomized Study of Adjuvant Erlotinib and Green Tea Extract (Polyphenon® E) in Preventing Recurrence and Progression in Former Smokers With Resected High-Grade Superficial Transitional Cell Carcinoma of the Bladder. Available at: http://www.cancer.gov/ clinicaltrials/UCLA-0301091-02. Accessed on August 5, 2005.
152. Bettuzzi A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in high grade PIN subjects: A preliminary report from a 1 year proof of principle study. Abstr. 4400. 96th Annual Meeting, AACR, Anaheim, CA, 2005.
153. Tun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci. 2001;16(Suppl):S3-S5.
154. Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev. 2004;9:259-274.
155. Yun T-K, Lee Y-S, Lee YH, et al. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci. 2001;16(Suppl)S6-S18.
156. Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci. 2002;16(Suppl):S28- S37.
157. Francis G, Kerem Z, Makkar HPS, et al. The biological action of saponins in animal systems: a review. Br J Med. 2002;88:587-605.
158. Park IH, Piao LZ, Kwon SW, et al. Cytotoxic dammarane glycosides from processed ginseng. Chem Pharm Bull. 2002; 50:538-540.
159. Chang YS, Seo E-K, Gyllenhaal C, et al. Panax ginseng: a role in cancer therapy? Integr Cancer Ther. 2003;2:13-33.
160. Surh Y-J, Na H-K, Lee J-Y, et al. Molecular mechanisms underlying anti-tumor promoting activities of heat-processes Panax ginseng C.A. Meyer. J Korean Med Sci. 2001;16(Suppl):S38-S41.
161. Liu ZQ, Luo XY, Lui GZ, et al. In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem. 2003;51:2555-2558.
162. Liu ZQ, Luo XY, Sun YX, et al. Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis? Biochim Biophys Acta. 2002;1572:58-66.
163. Keum YS, Han SS, Chun KS, et al. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res. 2003;523-524:75-85.
164. Oh GS, Pae HO, Choi BM, et al. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett. 2004;205:23-29.
165. Duda RB, Kang S-S, Archer SY, et al. American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines. J Korean Med. 2001;16(Suppl):S54-S60.
166. Oh SH, Lee BH. A ginseng saponin metabolite-induced apoptosis in HepG2 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and Bid cleavage. Toxicol Appl Pharmacol 2004;194:221-229.
167. Kim SE, Lee YH, Park JH, et al. Ginsenoside-Rs4, a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells. Eur J Cancer. 1999;35:507-511.
168. Chen S-W, Li X-H, Ye K-H, et al. Total saponins of Panax notoginseng protected rabbit iliac artery against balloon endothelial denudation injury. Acta Pharmacol Sin. 2004;25:1151-1156.
169. Kim SW, Kwon HY, Chi DW, et al. Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3). Biochem Pharmacol. 2003;65:75-82.
170. Choi C-H, Kang G, Min Y-D. Reversal of p-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng. Planta Med. 2003;69:235-240.
171. Fukushima S, Wanibuchi H, Li W. Inhibition by ginseng of colon carcinogenesis in rats. J Korean Med Sci. 2001;16(Suppl):S75-S80.
172. Wargovich MJ. Colon cancer chemoprevention with ginseng and other botanicals. J Korean Med Sci. 2001;16(Suppl):S81-S86.
173. Bespalov VG, Alexandrov VA, Limarenko AY, et al. Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium. J Korean Med Sci. 2001;16(Suppl):S42-S53.
174. Nishino H, Tokuda H, Ii T, et al. Cancer chemoprevention by ginseng in mouse liver and other organs. J Korean Med Sci. 2001;16(Suppl):S66-S69.
175. Wu X-G, Zhu D-H, Li X. Anticarcinogenic effect of red ginseng on the development of liver cancer induced by diethylnitrosamine in rats. J Korean Med Sci. 2001;16(Suppl):S61-S65.
176. Vanisree M, Lee C-Y, Lo S-F, et al. Studies on the production of some important secondary metabolites from medicinal plants by plant tissue cultures. Bot Bull Acad Sin. 2004;45:1-22.
177. Cogo E, Lai K. Should ginseng be considered for cancer prevention? Univ Toronto Med J. 2003;80:153-155.
178. Yun T-K, Hoi S-Y, Yun HY. Epidemiological study on cancer prevention by ginseng: Are all kinds of cancers preventable by ginseng? J Korean Med Sci. 2001;16(Suppl):S19-S27.
179. Yun T-K, Choi S-Y. Non-organ specific cancer prevention of ginseng: A prospective study in Korea. Int J Epidemiol. 1998;27:359-364.
180. Yun TK, Choi SY. Preventive effect of ginseng intake against various human cancers: A case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 1995;4:401-408.
181. Yun TK, Choi SY. A case control study of ginseng intake and cancer. Int J Epidemiol. 1990;19:871-876.
182. Yun TK, Choi SY. Non organ specific cancer prevention of ginseng: A prospective study in Korea. Int J Epidemiol. 1998;27:359-364.
183. Meletis CD, Barker JE. Medicinal mushrooms. Altern Complement Med. 2005;11:141-145.
184. Smith JE, Rowan NJ, Sullivan R. Medicinal Mushrooms: Their Therapeutic Properties and Current Medicinal Usage with Special Emphasis on Cancer Treatment. United Kingdom: Cancer Research, UK; 2002.
185. Daba AS, Ezeronye OU. Anti-cancer effect of polysaccharides isolated from higher basidiomycetes mushrooms. Afr J Biotechnol. 2003;2:672-678.
186. Silva D. Ganoderma lucidum (reishi) in cancer treatment. Integrative Cancer Therapies. 2003;2:358-364.
187. Kulicke WM, Lettau AI, Thielking H. Correlation between immunological activity, molecular mass, and molecular structure of different (1 → 3)-beta-D-glucans. Carbohydr Res. 1997;297:135-143.
188. Lin Z-B, Zhang H-N. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin. 2004;25:1387-1395.
189. Kohguchi M, Kunikata T, Watanabe H, et al. Immuno-potentiating effects of the antler-shaped fruiting body of Ganoderma lucidum (rokkaku-reishi). Biosci Biotechnol Biochem. 2004;68:881-887.
190. Lin S-B, Li C-H, Lee S-S, et al. Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle. Life Sci. 2003;72:2381-2390.
191. Gao J-J, Min B-S, Ahn E-M, et al. New triterpene aldehydes, lucialdehydes A-C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull. 2002;50:837-840.
192. Lu Q-Y, Sartippour MR, Brooks MN, et al. Ganoderma lucidum spore extract inhibits endothelial and breast cancer cells in vitro. Oncol Rep. 2004;12:659-662.
193. Gao Y, Zhou S, Jiang W, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 2003;32:201-215.
194. Gao Y, Tang W, Dai X, et al. Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer. J Med Food. 2005;8:59-168.
195. Seifried HE, McDonald SS, Anderson DE, et al. The antioxidant conundrum in cancer. Cancer Res. 2003;63:4295-4298.
196. Lamson DW, Brignall MS. Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Altern Med Rev. 1999;4:304-329.
197. Dröge W. Free radicals in physiological control of cell function. Physiol Rev. 2002;82:47-95.
198. Morel Y, Barouki R. Repression of gene expression by oxidative stress. Biochem J. 1999;342:481-496.
199. Kern JC, Kehrer JP. Free radicals and apoptosis: relationships with glutathione, thioredoxin and the bel family of proteins. Frontiers Biosci. 2005;10:1727-1738.
200. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10:709-720.
201. Suzuki TJ, Forman HJ, Sevanian A. Oxidants as stimulators of signal transduction. Free Rad Biol Med. 1997;22:269-285.
202. Nakamura H, Nakamura K, Yodoi J. Redox regulation of cellular activation. Annu Rev Immunol. 1997;15:351-369.
203. Storz P. Reactive oxygen species in tumor progression. Frontiers Biosci. 2005;10:1881-1896.
204. Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Rad Biol Med. 2000;28:1387-1404.
205. Schoonbroodt S, Piette J. Oxidative stress interference with the nuclear factor-κB activation pathways. Biochem Pharmacol. 2000;60:1075-1082.
206. Davis W, Ronai Z, Tew KD. Cellular thiols and reactive oxygen species in drug-induced apoptosis. JPET. 2001;296:1-6.
207. Shacter E, Williams JA, Hinson RM, et al. Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis. Blood. 2000;96:307-313.
208. Conklin KA. Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004;3:294-300.
209. Prasad KN, Cole WC, Kumar B, et al. Scientific rationale for using high-dose multiple micronutrients as an adjunct to standard and experimental cancer therapies. J Am Coll Nutr. 2001;20:450S-463S.
210. Lamson DW, Brignal MS. Antioxidants and cancer therapy II: Quick reference guide. Altern Med Rev. 2000;5:152-163.
211. Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr. 2001;5:464S-472S.
212. Prasad KN. Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. Integr Cancer Ther. 2004;3:310-322.
213. Prasad KN, Mumar A, Kochupillai V, et al. High doses of multiple antioxidant vitamins: Essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr. 1999;18:13-25.
214. Prasad KN, Kumar B, Yan X-D, et al. α-Tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: A review. J Am Coll Nutr. 2003;22:108-117.
215. Lansky EP, Jiang W, Mo H, et al. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest New Drugs. 2005;23:11-20.
216. Newman RA, Lansky EP, Reed C, et al. Punicic acid: A putative chemopreventive agent isolated from pomegranates. Abstr. 65. Society for Integrative Oncology, 1st International Conference, 2004:57.
217. Mehata R, Lansky EP. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev. 2004;13:345-348.
218. Albrecht M, Jiang W, Kumi-Diaka J, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004;7:274-283.
219. Kawaii S, Lansky EP. Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells. J Med Food. 2004;7:13-18.
220. Toi M, Bando H, Ramachandran C, et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis. 2003;6:121-128.
221. Lansky EP, Harrison G, Froom P, et al. Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel. Invest New Drugs. 2005;23:121-122.
222. Kiyohara H, Matsumoto T, Yamada H. Combination effects of herbs in a multi-herbal formula: Expression of Juzen-taiho-to's immuno-mudulatory activity on the intestinal immune system. Evidenced-Based Complementary and Alternative Medicine. 2004;1:83-91.
223. Capodice JL, Bemis DL, Buttyan R, et al. Zyflamend™, a unique herbal preparation inhibits arachidonic acid metabolism and suppresses prostate cancer cells. Abstr. 71. Society for Integrative Oncology, 1st International Conference, 2004:59.
224. Vickers AJ, Kup J. Botanicals, vitamins, dietary supplements for improving survival in cancer: A systemic review of prospective clinical trials. Abstr. 63. Society for Integrative Oncology, 1st International Conference, 2004:55.
225. Linde K, Riet G, Hondras M, et al. Systematic reviews of complementary therapies: An annotated bibliography. Part 2: Herbal medicine. BMC Complementary and Alternative Medicine. 2001;1:5-16.
226. Vickers AJ, Kattan M, Gonen M. Design of phase I and phase II trials of anticancer botanicals. Abstr. 78. Society for Integrative Oncology, 1st International Conference, 2004:62.
227. Ernst E. Equivalence and non-inferiority trials of CAM. Evidenced-Based Complementary and Alternative Medicine. 2004;1:9-10.
228. Tripathy D. Keynote talk: The role of cancer programs in translational research for integrative medicine. Society for Integrative Oncology, 1st International Conference, 2004.
229. Randal J. Diagnosis, Tibetan style, underlies small herbal study of advanced breast cancer. JNCI. 1999;91:587-588.
230. Myers C, Stuber ML, Bonamer-Rheingans JI, et al. Complementary therapies and childhood cancer. Cancer Control. 2005;12:172-180.
231. Kelly KM, Jacobson JS, Kennedy DD, et al. Use of unconventional therapies by children with cancer at an urban medical center. J Pediatr Hematol Oncol. 2000;22:412-416.
232. Kelly KM. Complementary and alternative medical therapies for children with cancer. Eur J Cancer. 2004;40:2041-2046.
233. Mottonen M, Uhari M. Use of micronutrients and alternative drugs by children with acute lymphoblastic leukemia. Med Pediatr Oncol. 1997;28:205-208.