The anti-cancer charm of flavonoids: A cup-of-tea will do!

Recent Patents on Anti-Cancer Drug Discovery

Volumn 2, Issue 2, 2007, Pages 109-117

  Amin, Amr ^a   Buratovich, Michael ^b  

^a UNITED ARAB EMIRATES UNIVERSITY   (United Arab Emirates)

^b SPRING ARBOR UNIVERSITY   (United States)

Author keywords

Cancer; Coumestans; Estrogen; Flavonoids; Isoliquiritigenin; Lignans; Phytoestrogen; Stilbenes; Wogonin

Indexed keywords

ALPHA TOCOTRIENOL; BIOCHANIN A; BIOFLAVONOID; CATECHIN; COUMARIN DERIVATIVE; DAIDZEIN; EQUOL; ESTRADIOL; FLAVANONE DERIVATIVE; FLAVONE DERIVATIVE; FLAVONOID; FORMONONETIN; GENISTEIN; GINKGO BILOBA EXTRACT; GLYCITEIN; HESPERETIN; LIGNAN; NARINGENIN; NOBILETIN; PHYTOESTROGEN; POLYPHENOL DERIVATIVE; QUERCETIN; RALOXIFENE; RESVERATROL; SAPONIN DERIVATIVE; STILBENE DERIVATIVE; TAMOXIFEN; TANGERETIN; TANNIN DERIVATIVE; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; BREAST CANCER; CANCER; CANCER RISK; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; COLORECTAL CANCER; DIET SUPPLEMENTATION; DIETARY INTAKE; DRUG BLOOD LEVEL; DRUG CLASSIFICATION; DRUG EFFECT; DRUG EFFICACY; DRUG ISOLATION; DRUG MECHANISM; DRUG METABOLISM; DRUG PURIFICATION; DRUG STRUCTURE; DRUG TRANSPORT; ENDOMETRIUM CANCER; FLOWER; FOOD COMPOSITION; GENETIC CODE; GENETIC RISK; HUMAN; HYPERCHOLESTEROLEMIA; NONHUMAN; PARKINSON DISEASE; PLANT LEAF; PLANT ROOT; PLANT SEED; PLANT STEM; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DETERMINATION; PROTEIN FUNCTION; REVIEW; RISK ASSESSMENT; RISK FACTOR; RISK REDUCTION; SKIN INFLAMMATION; TEA; THROMBOCYTE AGGREGATION INHIBITION;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; FLAVONOIDS; HUMANS; MOLECULAR STRUCTURE; NEOPLASMS, HORMONE-DEPENDENT; PATENTS AS TOPIC; RECEPTORS, ESTROGEN; SIGNAL TRANSDUCTION;

EID: 34250768309     PISSN: 15748928     EISSN: None     Source Type: Journal    
DOI: 10.2174/157489207780832414     Document Type: Review

References (171)

1. Facchini PJ. Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation and metabolic engineering. Ann Rev Plant Physiol Plant Mol Biol 2001; 52: 29-66.
2. Holstein SA, Hohl RJ. Isoprenoids: remarkable diversity of form and function. Lipids 2004; 34: 293-309.
3. Iriti M, Faoro F. Plant defense and human nutrition: the phenylpropanoids on the menú, Curr Top Nutr Res 2004; 2: 47-65.
4. Kasbia GS. Functional foods and nutraceuticals in the management of obesity. Nutr Food Sci 2005; 35: 344-52.
5. Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis 2000; 21: 427-33.
6. Meegan MJ, Lloyd DG. Advances in the science of estrogen receptor modulation. Curr Med Chem 2003; 10: 181-210.
7. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators-mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618-29.
8. Cornwell T, Cohick W, Raskin I. Dietary phytoestrogens and health. Phytochemistry 2004; 65: 995-1016.
9. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry 2000; 55: 481-504.
10. Hays J, Ockene JK, Brunner RL, et al. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003; 348: 1835-37.
11. Toft D, Gorski J. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci USA 1966; 55 (6): 1574-81.
12. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 1995; 83(6): 835-39.
13. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93 (12): 5925-30.
14. Bodo C, Rissman EF. New roles for estrogen receptor β a behavior and neuroendocrinology. Front Neuroendocrinol 2006; 27(2): 217-32.
15. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S. Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol 1998; 54 (1): 105-12.
16. Kuiper GG, Carlsson B and Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997; 138 (3): 863-70.
17. Matthews J and Gustafsson JA. Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol Interv 2003; 3(5): 281-92.
18. Valimaa H, Savolainen S, Soukka, T, et al. Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J Endocrinol 2004; 180 (1): 55-62.
19. Hiroi H, Inoue S, Watanabe T, et al. Differential immunolocalization of estrogen receptor alpha and beta in rat ovary and uterus. J Mol Endocrinol 1999; 22(1): 37-44.
20. Nilsson S, Gustafsson JA. Biological role of estrogen and estrogen receptors. Crit Rev Biochem Mol Biol 2002; 37: 1-28.
21. Macgregor JI, Jordan VC. Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 1998; 50: 151-96.
22. Gustafsson JA. What pharmacologists can learn from recent advances in estrogen signalling. Trends Pharmacol Sci 2003; 24: 479-85.
23. Cody V, Middleton E, Harborne JB. Plant Flavonoids in Biology and Medicine. Alan R. Liss, New York 1986.
24. Tian J, Liu J, Hu Z, Chen X. Interaction of wogonin with bovine serum albumin. Bioorganic & Medicinal Chemistry, In Press. Available online 25 April 2005.
25. Chen S, Hwang J, Deng PSK. Inhibition of NAD(P)H:Quinone acceptor oxidoreductase by flavones: A structure-activity study. Arc Biochem Biophys 1993; 302: 72-77.
26. Peterson J, Dwyer J. Flavonoids: dietary occurrence and biochemical activity. Nutr Res 1998; 18: 1995-2018.
27. Stopper H, Schmitt E, Kobras K. Genotoxicity of phytoestrogens. Mutat Res 2005, 574(1-2): 139-55.
28. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851-74.
29. Kühnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nutr Diet 1976; 24: 117-91.
30. Lephart E, Setchell K, Lund T. Phytoestrogens: hormonal action and brain plasticity. Brain Res Bull 2005; 65: 193-98.
31. Adlercreutz H. Epidemiology of phytoestrogens. Bailieres, Clin Endocrinol Metab 1998; 12: 605-23.
32. Adlercreutz H. Evolution, nutrition, intestinal microflora, and prevention of cancer: A hypothesis. Proc Soc Exp Biol Med 1997; 217: 241-46.
33. Adlercreutz H, Mazur W. Phyto-estrogens and western diseases. Ann Med 1997; 29: 95-120.
34. Barnes S. Evolution of the health benefits of soy isoflavones. Proc Soc Exp Biol Med 1998; 217: 386-92.
35. Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med 2001; 161: 1161-72.
36. Kurzer MS, Xu X. Dietary phytoestrogens. Ann Rev Nutr 1997; 17: 353-81.
37. Patisaul HB, Whitten PL. Dietary phytoestrogens. In: R.K. Naz, Editor, Endocrine Disruptors, CRC Press, New York, NY 1998; 100-23.
38. Setchell KDR. Soy isoflavones-benefits and risks from nature's selective estrogen receptor medulators (SERMs). J Am Coll Nutr 2001; 20: 354S-83S.
39. Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause? Mayo Clin Proc 2000; 75: 1174-84.
40. De Vries GJ. Minireview: sex differences in adult and developing brains: compensation, compensation, compensation. Endocrinology 2004; 145: 1063-68.
41. Faber KA, Hughes Jr. CL. The effect of neonatal exposure to diethylstilbestrol, genistein, and zearalenone on pituitary responsiveness add sexually dimorphic nucleus volume in the castrated adult rat. Biol Reprod 1991; 45: 649-53.
42. Faber KA, Hughes Jr. CL. Dose-response characteristics of neonatal exposure to genistein on pituitary, responsiveness to gonadotropin releasing hormone and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in postpubertal castrated female rats. Reprod Toxicol 1993; 7: 35-39.
43. Lechner D, Kállay, E, CrossH. Phytoestrogens and Colorectal Cancer. Vitam Horm 2005; 70: 169-98.
44. Dotsch J, Dorr HG, Wildt L. Exposure to Endogenous Estrogens During Lifetime. Endocrine Disruptors Part I. M. Metzler. Berlin Heidelberg, Springer-Verlag 2001; 83-99.
45. Bennetts HW, Underwood EJ, Shier FL. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust Vet J 1946; 22: 2-12.
46. Rossiter RC, Beck AB. Physiological and ecological studies on the estrogenic isoflavones in subterranean clover (Trifolium subterraneum) I. Effects of temperature. Aust J Agric Res 1966; 17: 29-37.
47. Adlercreutz H, Mousavi Y, Clark J, et al. Dietary phytoestrogens and cancer: in vitro and in vivo studies. J Steroid Biochem Mol Biol 1992; 41: 331-37.
48. Pino AM, Valladares LE, Palma MA, Mancilla AM, Yanez M, Albala C. Dietary isofalvones affect sex hormone-binding globulin levels in postmenopausal women. J Clin Endocrinol Metab 2000; 85: 2797-800.
49. Berrino F, Bellati C, Secreto G, et al. Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 2001; 10: 25-33.
50. Hutchins AM, Martini MC, Olson BA, Thomas W, Slavin JL. Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women. Nutr Cancer 2001; 39: 58-65.
51. Xu X, Duncan AM, Wangen KE, Kurzer MS. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol. Biomarkers Prev 2000; 9: 781-86.
52. Lu LJW, Anderson KE, Grady JJ, Nagamani M. Effects of an isoflavone-free soy diet on ovarian ovarian hormones in premenopausal women. J Clin Endocrinol Metab 2001; 86: 3045-52.
53. Xu X, Duncan AM, Merz BE, Kurzer MS. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 1998; 7: 1101-08.
54. Haggans CJ, Hutchins AM, Olson BA, Thomas W, Martini MC, Slavin JL. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer 1999; 33: 188-95.
55. Lephart ED, Setchell KDR, Lund TD. Phytoestrogens: hormonal action and brain plasticity Brain Research Bulletin 2005; 65: 193-98.
56. Beck V, Rohr U, Jungbauer A. Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy? J Steroid Biochem Mol. Biol 2005; 94: 499-518.
57. Tominaga S, Kuroishi T. Epidemiology of Breast Cancer in Japan. Breast Cancer 1995; 2: 1-7.
58. Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA. Phytoestrogen concentrations in serum from Japanese men and women over 40 years of age. J Nutr 2002; 132: 3168-71.
59. Lawson JS, Field AS, Champion S, Tran D, Ishikura H, Trichopoulos D. Low oestrogen receptor alpha expression in normal breast tissue underlies low breast cancer incidence in Japan. Lancet 1999; 354: 1787-88.
60. Deapen D, Liu L, Perkins C, Bernstein L, Ross RK. Rapidly rising breast cancer incidence rates among Asian-American women. Int J Cancer 2002; 99: 747-50.
61. Pineda MD, White E, Kristal AR, Taylor V. Asian breast cancer survival in the US: a comparison between Asian immigrants, US-born Asian Americans and Caucasians. Int J Epidemiol 2001; 30: 976-82.
62. Minami Y, Ohuchi N, Fukao A, Hisamichi S. Determinants of infant feeding method in relation to risk factors for breast cancer. Prev Med 2000; 30: 363-70.
63. Adlercreutz H. Phytoestrogens and breast cancer. J Steroid Biochem Mol Biol 2002; 83: 113-18.
64. Beck V, Rohr U, Jungbauer A. Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy?. J Steroid Biochem 2005; 94: 499-518.
65. Stopper H, Schmitt E, Kobras K. Genotoxicity of phytoestrogens. Mutat Res 2005; 574: 139-55.
66. Whitten P, Patisaul H. Cross-species and interassay comparisons of phytoestrogen action. Environ Health Perspect 2001; 109: 5-20.
67. Cardoso JR, Báo SN. Effects of chronic exposure to soy meal containing diet or soy derived isoflavones supplement on semen production and reproductive system of male rabbits, 2006; Animal Reproduction Science, Available online 13 March 2006, at, last accessed 9/28/2006.
68. Morton MS, Chan PS, Cheng S, et al. Lignans and isoflavonoids in plasma and prostatics fluid in men: samples from Portugal, Hong-Kong and the United Kingdom. Prostate 1997; 32: 122-28.
69. Rosenberg Zand RS, Jenkins DJ, Brown TJ, Diamandis EP. Flavonoids can block PSA production by breast and prostate cancer cell lines. Clin Chim Acta 2002; 317: 17-26.
70. Tolcher AW, Kennedy A, Padley RJ, Majeed N, Pollak M, Kantoff PW. Other novel agents: rationale and current status as chemopreventive age. Urology 2001; 57: 86-89.
71. Landstrom M, Zhang JX, Hallmans G, et al. Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats. Prostate 1998; 1-36: 151-61.
72. Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr 1999; 129: 1628-35.
73. Bylund A, Zhang JX, Bergh A, et al. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. Prostate 2000; 42: 304-14
74. Nagata C, Inaba S, Kawakami N. Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men. Nutr Cancer 2000; 36: 14-18.
75. Kuiper GG, Carlsson B, Grandien K. Cloning of a novel estrogen receptorexpressed in a rat prostate and ovary. Proc Natl Acad Sci 1996; 93: 5925-30.
76. Barnes S. Role of phytochemicals in prevention and treatment of prostate cancer. Epidemiol Rev 2001; 23: 102-05.
77. Choi YH, Lee WH, Park KY, Zhang L. p53-independent induction of p21 [WAF1/CIP1], reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn J Cancer Res 2000; 91: 164-73.
78. Kobayashi T, Nakata T, Kuzumaki T. Effect of flavonoids on cell cycle progression in prostate cancer cells. Cancer Lett 2002; 176: 17-23.
79. Markiewicz L. In vivo bio assays of non-steroidal phytoestrogens. J Steroid Biochem Mol Biol 1993; 45: 399-405.
80. Kirk CJ, Harris RM, Wood DM, Waring RK, Hughes PJ. Do dietary phytoestrogens influence susceptibility to hormone-dependent cancer by disrupting the metabolism of endogenous oestrogens?. Biochem Soc Trans 2001; 29: 209-16.
81. Adlercreutz H. Phystoestrogens and cancer. Lancet Oncol 2002; 3: 364-73.
82. Sarker FH, Li Y. Mechanism of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev 2002; 21: 265-80.
83. Fritz WA, Eltoum IE, Cotroneo MS, Lamartiniere CA. Genistein alters growth but is not toxic to the rat prostate. J Nutr 2002; 132: 3007-3011.
84. Castle EP, Thresher JB. The role of soy phytoestrogen in prostate cancer. Urol Clin North Am 2002; 29: 71-81.
85. Adlercreutz H, Mazur W, Bartels P, et al. Phytoestrogen and prostate disease. J Nutr 2000; 130: 658S-59S.
86. Ganry O. Phytoestrogens and prostate cancer risk. Prev Med 2005 41(1): 1-6.
87. Liu J, Burdette JE, Xu H. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem 2001; 49: 2472-79.
88. Davis JN, Kucuk O, Sarker FH. Expression of prostate-specific antigen is transcriptionally regulated by genistein in prostate cancer cells. Mol Carcinog 2002; 34: 91-101.
89. Wang D, Gutkowska J, Marcinkiewicz M, Rachelska G, Jankowski M. Genistein supplementation stimulates the oxytocin system in the aorta of ovariectomized rats. Cardiovasc Res 2003; 57: 186-94.
90. Zhou S, Turgeman G, Harris Stephen E, et al. Estrogens activate bone morphogenetic protein-2 gene transcription in mouse mesenchymal stem cells. Mol Endocrinol 2003; 17: 56-66.
91. American Institute for Cancer Research, 1997. Food Nutrition and the Prevention of Cancer: A Global Perspective, World Cancer Research Fund, Washington.
92. Kelly, G.E.: US20066987098 (2006).
93. Dixon RA, Ferreira D. Ganistein. Phytochemistry 2002; 60: 205-11.
94. Nakayama, T., Sawada, S., Suzuki H., Nishino, T.: WO6016395A1(2006).
95. Bedoya LM, del Olmo E, Sancho R, et al. Anti-HIV activity of stilbene-related heterocyclic compounds. Bioorg Med Chem Lett 2006; 16(15): 4075-9.
96. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA 1997; 94: 14138-43.
97. Creasy LL, Creasy MT. Grape chemistry and the significance of resveratrol: An Overview. Pharm Biol 1998; 36: 8-14.
98. Sobolev VS, Cole RJ. trans-Resveratrol content in commercial peanuts and peanut products. J Agric Food Chem 1999; 47: 1435-39.
99. Sanders TH, Robert W, McMichael J, Hendrix KW. Occurrence of resveratrol in edible peanuts. J Agric Food Chem 2000; 48: 1243-46.
100. Vastano BC, Chen Y, Zhu N, Ho CT, Zhou Z, Rosen RT. Isolation and identification of stilbenes in two varieties of Polygonum cuspidatum. J Agric Food Chem 2000; 48: 253-56.
101. Powell RG, TePaske MR, Plattner RD, White JF, Clement SL. Isolation of reveratrol from Festuca versula and evidence for the widespread occurrence of this stilbene in the poaceae. Phytochemistry 1994; 35: 335-38.
102. Mannila E, Talvitie A. Stilbenes from Picea abies bark. Phytochemistry 1992; 31: 3288-89.
103. Klinge CM, Risinger KE, Watts MB, Beck V, Eder R, Jungbauer A. Estrogenic activity in white and red wine extracts. J Agric Food Chem 2003; 51: 1850-57.
104. Lu R, Serrero G. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J Cell Physiol 1999; 179: 297-304.
105. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000; 141: 3657-67.
106. Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ. Flavonoid effects relevant to cancer. J Nutr 2002; 132: 3482S-89S.
107. Frankel EN, Waterhouse AL and Kinsella JE. Structural basis for DNA-cleaving activity of resveratrol in the presence of Cu(II). Lancet 1993; 341: 1103-1104.
108. Belguendouz L, Fremont L, Linard A. Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. Biochem Pharmacol 1997; 53: 1347-55.
109. Jang M, Pezzuto JM. Cancer chemopreventive activity of resveratrol. Drugs Exp Clin Res 1999; 25: 65-77.
110. Olas B, Wachowicz B, Stochmal A, Oleszek W. Anti-platelet effects of different phenolic compounds from Yucca schidigera Roezl. Bark. Platelets 2002; 13: 167-73.
111. Wu JM, Wang ZR, Hsieh TC, Bruder KL, Zou LG, Huang YZ. Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review). Int J Mol Med 2001; 8: 3-17.
112. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol a natural product derived from grapes. Science 1997; 275: 218-20.
113. Mgbonyebi OP, Russo J, Russo IH. Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int J Oncol 1998; 12: 865-69.
114. Uenobe F, Nakamura S, Miyazawa M. Antimutagenic effect of resveratrol against Trp-P-1. Mutat Res 1997; 373: 197-200.
115. Kim HJ, Chang EJ, Bae SJ, et al. Cytotoxic and antimutagenic stilbenes from seeds of Paeonia lactiflora. Arch Pharm Res 2002; 25: 293-99.
116. Fukuhara K, Nagakawa M, Nakanishi I, et al. Structural basis for DNA-cleaving activity of resveratrol in the presence of Cu(II). Bioorg Med Chem 2006; 14(5): 1437-43.
117. Peñalvo JL, Nurmi T. Application of coulometric electrode array detection to the analysis of isoflavonoids and lignans. J Pharm Biomed Anal 2006; 41(5): 1497-507.
118. Pietinen P, Stumpf K, Mannisto S, Kataja V, Uusitupa M, Adlercreutz H. Serum enterolactone and risk of breast cancer: a case-control study in Eastern Finland. Cancer Epidemiol Biomarkers Prev 2001; 10: 339-44.
119. Boccardo F, Lunardi G, Guglielmini P, et al. Serum enterolactone levels and the risk of breast cancer in women with palpable cysts. Eur J Cancer 2004; 40: 84-89.
120. Horn-Ross PL, Hoggatt KJ, Lee MM. Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomarkers Prev 2002; 11: 43-49.
121. McCann SE, Freudenheim JL, Marshall JR, Graham S. Risk of human ovarian cancer is related to dietary intake of selected nutrients, Phytochemicals and Food Groups. J Nutr 2003; 133:1937-42.
122. Lee H.P, Gourley L, Duffy SW, Esteve J, Lee J, Day NE. Dietary effects on breast-cancer risk in Singapore. Lancet 1991; 337: 1197-200.
123. McCann SE, Moysich KB, Freudenheim JL, Ambrosone CB, Shields PG. The risk of breast cancer associated with dietary lignans differs by CYP17 genotype in women. J Nutr 2002; 132: 3036-41.
124. Horn-Ross PL, Hoggatt KJ, West DW, et al. Recent diet and breast cancer risk: the California Teachers Study (USA). Cancer Cause Control 2002; 13: 407-15.
125. Kilkkinen A, Virtamo J, Vartiainen E, et al. Serum enterolactone concentration is not associated with breast cancer in a nested case control study. Int J Cancer 2004; 108: 277-80.
126. Messina MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. J Nutr 2001; 131: 3095S-108S.
127. Power KA, Ward WE, Chen JM, Saarinen NM, Thompson LU. Genistein alone and in combination with the mammalian lignans enterolactone and enterodiol induce estrogenic effects on bone and uterus in a postmenopausal breast cancer mouse model. Bone 2006; 39(1): 117-24.
128. Vanharanta M, Voutilainen S, Nurmi T, et al. Association between low serum enterolactone and increased plasma F2-isoprostanes, a measure of lipid peroxidation. Atherosclerosis 2002; 160: 465-69.
129. Vanharanta M, Voutilainen S, Rissanen TH, Adlercreutz H, Salonen JT. Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med 2003; 163: 1099-104.
130. Pietinen P, Stumpf K, Mannisto S, Kataja V, Uusitupa M, Adlercreutz H. Serum enterolactone and risk of breast cancer: a case-control study in eastern Finland. Cancer Epidemiol Biomarkers Prev 2001; 10: 339-44.
131. Knuckles BE, DeFremery D, Kohler GO. Coumestrol content of fractions obtained during wet processing of alfalfa. J Agric Food Chem 1976; 24: 1177-80.
132. Wang GS, Kuan S, Francis OJ, Waze GM, Carman AS. A simplified HPLC method for the determination of phytoestrogens in soybean and its processed products. J Agric Food Chem 1990; 38: 185-90.
133. Franke AA, Custer LJ, Cerna CM, Narala KK. Quantitation of phytoestrogens in legumes by HPLC. J Agric Food Chem 1994; 42: 1905-13.
134. Blomquist CH, Lima PH, Hotchkiss JR. Inhibition of 3α-hydroxysteroid dehydrogenase (3α-HSD) activity of human lung microsomes by genistein, daidzein, coumestrol and C18-, C19- and C21-hydroxysteroids and ketosteroids. Steroids 2005; 70(8): 507-14.
135. Matsumura A, Ghosh A, Pope GS, Darbre PD. Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells. J Steroid Biochem 2005; 94: 431-43.
136. Gutierrez-Uribe, J.A., Serna-Saldivar, S.R.O., Moreno-Cuervas, J.E., Hernandez-Brenes, C., Guajardo-Touche, E.M.: US20060024394A1 (2006).
137. Gutierrez-Uribe, J.: WO05107780A2 (2005).
138. Chi YS, Kim HP. Suppression of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix. Prostaglandins Leukot Essent Fatty Acids 2005; 72(1): 59-66.
139. Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages. Eur J Pharmacol 2000; 406:477-81.
140. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol 1999; 58: 759-65.
141. Chi YS, Cheon BS, Kim HP. Effect of wogonin, a plain flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem Pharmacol 2001; 61: 1195-203.
142. Park BK, Heo MY, Park H, Kim HP. Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur J Pharmacol 2001; 425: 153-57.
143. Chi YS, Lim H, Park H, Kim HP. Effect of wogonin, a plant flavone from Scutellaria radix, on skin inflammation in vivo regulation of inflammation associated gene expression. Biochem Pharmacol 2003; 66: 1271-78.
144. Chi YS, Kim HP. Suppression-of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix. Prostag Leukotr Ess 2005; 72: 59-66.
145. Himeji M, Ohtsuki T, Fukazawa H. et al. Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell. Cancer Lett 2006; Available on line at http://www.sciencedirect.com/ science?_ob=ArticleURL&_udi=B6T54-4JB9W20-2&_coverDate= 02%2F23%2F2006/&_alid=-457728312&_rdoc= 1&_fint=&_orig=search&_qd-1&_cdi= 4992&_sort=d&view=c&_acct=C000050221&_version= 1&_urlVersion=0&_userid=10&md5=44cb8e17f9e09e76074 56835b9436c15, last accessed 9/28/2006.
146. Vaya J, Belinky PA, Aviram M. Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation. Free Radical Bio Med 1997; 23: 302-13.
147. Chan SC, Chang YS, Wang JP, Chen SC, Kuo SC. Three new flavonoids and antiallergic anti-inflammatory constituents from the heartwood of Dalbergia adorifera. Plants Med 1998; 64: 153-58.
148. Tawata M, Aida K, Noguchi T. Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J Pharmacol 1992; 212: 87-92.
149. Baba M, Asano R, Takigami I, et al. Studies on cancer chemoprevention by traditional folk medicines XXV. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis. Biol Pharm Bull 2002; 25: 247-50.
150. Yamamoto S, Aizu E, Jiang H, et al. The potent anti-tumor promoting agent isoliquiritigenin. Carcinogenesis 1991; 12: 317-23.
151. Yamazaki S, Morita T, Endo H. et al. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett. 2002; 183: 23-30.
152. Kanazawa M, Satomi Y, Mizutani Y et al. Isoliquiritigenin inhibits the growth of prostate cancer. Eur Urol 2003; 43: 580-86.
153. Maggiolini M, Statti G, Vivacqua A, et al. Estrogenic and antiproliferative activities isoliquiritigenin in MCF7 breast cancer cells. J Steroid Biochem 2002; 82: 315-22.
154. Ma J, Fu NY, Pang DB, Wu WY, Xu AL. Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Medica 2001; 67: 754-57.
155. Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci Biotech Bioch 2000; 64: 1813-20.
156. Takahashi T, Takasuka, N, Iigo M, et al. Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci 2004; 95: 448-53.
157. Takahashi T, Baba M, Nishino H, Okuyama T. Cyclooxygenase-2 plays a suppressive role for induction of apoptosis in isoliquiritigenin-treated mouse colon cancer cells. Cancer Lett 2006; 231(2): 319-25.
158. Hsu YL, Kuo PL, Lin CC. Isoliquiritigenin induces apoptosis and cell cycle arrest through p53-dependent pathway in Hep G2 cells. Life Sci 2005; 77: 279-292.
159. Tseng TH, Lee YJ. Evaluation of natural and synthetic compounds from East Asiatic folk medicinal plants on the mediation of cancer. Anticancer Agents Med Chem. 2006 6(4): 347-65.
160. Martens S, Mithofer A. Flavones and flavone synthases. Phytochemistry. 2005; 66(20): 2399-407.
161. Guthrie, N.: US2006013901A1 (2006).
162. Guthrie, N.: US2006013902A1 (2006).
163. Guthrie, N.: WO05115377A1 (2005).
164. Guthrie, N., Kurowska E.M., Manthey J.A., Horowitz S., Horowitz R.M.: US20006987125 (2000).
165. Kwak, W., Cho, Y., Han, C., Shin, H.J., Ryu, K.H., Yoo, H., Rhee, H.I.: US20060014240A1 (2006).
166. Rojas, C.N.: WO06004386A1 (2006).
167. Romanczyk, L.J., Schmitz, H.H.: US20066998417 (2006).
168. Fang Y. Label-free cell-based assays with optical biosensors in drug discovery. Assay Drug Dev Technol 2006; 4(5): 583-95.
169. Cooper M.A. Non-optical screening platforms: the next wave in Label-free screening? Drug Discov Today 2006; 11(23-24): 1068-74.
170. Koffas, M., Leonard, E., Yan, Y., Chemler, J.: US20060019334A1 (2006).
171. Koffas, M., Leonard, E., Yan, Y., Chemler, J: WO06010117A2 (2006).