Mechanisms of action of the soy isoflavone genistein: Emerging role for its effects via transforming growth factor β signaling pathways

American Journal of Clinical Nutrition

Volumn 68, Issue 6 SUPPL., 1998, Pages

  Kim, Helen ^a   Peterson, T Greg ^a   Barnes, Stephen ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Breast cancer; Cell cycle checkpoints; Chemoprevention; Estrogen; Genistein; Growth factors; Hemorrhagic telangiectasia; Isoflavone; Soy; Transforming growth factor 1; Tyrosine kinase inhibitor

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; DNA TOPOISOMERASE (ATP HYDROLYSING); EPIDERMAL GROWTH FACTOR RECEPTOR; ESTRADIOL; ESTROGEN; GENISTEIN; ISOFLAVONE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; TAMOXIFEN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA1;

ANGIOGENESIS; ATHEROSCLEROSIS; BEVERAGE; BREAST CANCER; CARDIOVASCULAR DISEASE; CELL CYCLE; CELL GROWTH; CONFERENCE PAPER; GROWTH INHIBITION; HUMAN; HUMAN CELL; MAMMAL CELL; NONHUMAN; OSTEOPOROSIS; PROSTATE CANCER; PROTEIN INTAKE; RENDU OSLER WEBER DISEASE; SIGNAL TRANSDUCTION; SOYBEAN; TUMOR CELL LINE;

ANIMALS; ANTICARCINOGENIC AGENTS; BREAST NEOPLASMS; CARDIOVASCULAR DISEASES; CELL DIVISION; FEMALE; GENISTEIN; HUMANS; MALE; PROSTATIC NEOPLASMS; PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TELANGIECTASIA, HEREDITARY HEMORRHAGIC; TRANSFORMING GROWTH FACTOR BETA;

GLYCINE MAX; MAMMALIA;

EID: 0031741785     PISSN: 00029165     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (102)

1. Tominaga S. Cancer incidence in Japanese in Japan, Hawaii, and western United States. Natl Cancer Inst Monogr 1985;69:83-92.
2. Severson RK, Nomura AMY, Grove JS, Stemmerman GN. A prospective study of demographics, diet and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 1989;49:1857-60.
3. Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE. Dietary effects of breast cancer risk in Singapore. Lancet 1991; 337:1197-200.
4. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 1991;63:963-6.
5. Messina M, Barnes S. Workshop report from the Division of Cancer Etiology, National Cancer Institute, National Institutes of Health: the role of soy products in reducing risks of certain cancers. J Natl Cancer Inst 1991;83:541-6.
6. Barnes S, Grubbs C, Setchell KDR, Carlson J. Soybeans inhibit mammary tumors in models of breast cancer. In: Pariza M, ed. Mutagens and carcinogens in the diet. Wiley-Liss, Inc, 1990;239-53.
7. Barnes S, Peterson TG, Grubbs C, Setchell KDR. Potential role of dietary isoflavones in the prevention of cancer. In: Jacobs MM, ed. Diet and cancer: markers, prevention and treatment. New York: Plenum Press, 1994:135-48.
8. Hawrylewicz EJ, Huang HH, Blair WH. Dietary soybean isolate and methionine supplementation affect mammary tumor progression in rats. J Nutr 1991;121:1693-8.
9. Coward L, Barnes NC, Setchell KDR, Barnes S. Genistein and daidzein, and their glycoside conjugates: anti-tumor isoflavones in soybean foods from American and Asian diets. J Agric Food Chem 1993;41:1961-7.
10. Wang H-J, Murphy P. Isoflavone content in commercial soybean foods. J Agric Food Chem 1994;42:1666-73.
11. Franke AA, Custer LJ, Cerna CC, Narala KK. Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine. Proc Soc Exp Biol Med 1995;208:18-26.
12. Setchell KDR, Borriello SP, Hulme P, Kirk DN, Axelson M. Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 1984;40:569-78.
13. Adlercreutz H. Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest Suppl 1990;201:3-23.
14. Lamartiniere CA, Moore JB, Brown NA, Thompson RA, Hardin MJ, Barnes S. Genistein suppresses mammary cancer in rats. Carcinogenesis 1995;16:2833-40.
15. Murrill W, Brown NM, Zhang J-X, Manzolillo P, Barnes S, Lamartiniere CA. Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 1996;17:1451-7.
16. Constantinou AI, Mehta RG, Vaughan A. Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones. Anticancer Res 1996;16:3293-8.
17. Brown NM, Lamartiniere CA. Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Health Perspect 1995;103:708-13.
18. Grubbs CJ, Farnell DR, Hill DL, McDonough KC. Chemoprevention of N-nitroso-N-methylurea-induced mammary cancers by pretreatment with 17 beta-estradiol and progesterone. J Natl Cancer Inst 1985;74:927-31.
19. Helferich WG. Paradoxical effects of the soy phytoestrogen genistein on growth of human breast cancer cells in vitro and in vivo. Am J Clin Nutr 1998;68:1524S-5S (abstr).
20. Barnes S, Peterson TG. Biochemical targets of the isoflavone genistein in tumor cell lines. Proc Soc Exp Med Biol 1995;208:103-8.
21. Peterson TG. Evaluation of the biochemical targets of genistein in tumor cells. J Nutr 1995;125:784S-9S.
22. Barnes S, Peterson TG, Coward L. Use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem 1995;22:181-7.
23. Peterson TG, Barnes S. Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and multi-drug resistance gene product. Biochem Biophys Res Commun 1991;179:661-7.
24. Peterson TG, Barnes S. Genistein inhibits both estrogen and growth factor stimulated proliferation of human breast cancer cells. Cell Growth Differ 1996;7:1345-51.
25. Peterson TG, Barnes S. Genistein and biochanin A inhibit the growth of human prostate cancer cells in culture but not epidermal growth factor receptor tyrosine phosphorylation. Prostate 1993;22:335-45.
26. Wang TT, Sathyamoorthy N, Phang JM. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 1996;17:271-5.
27. Zava DT, Duwe G. Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer 1997;27:31-40.
28. Panno ML, Salerno M, Pezzi V, et al. Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells. J Cancer Res Clin Oncol 1996;122:745-9.
29. Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987;262:5592-6.
30. Peterson TP, Barnes S. Genistein potently inhibits the growth of human primary breast epithelial cells: correlation with a lack of genistein metabolism. Mol Biol Cell 1994;5:384A (abstr).
31. Clark JW, Santos-Moore A, Stevenson LE, Frackelton AR Jr. Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. Int J Cancer 1996;65:186-91.
32. Wright JD, Reuter CW, Weber MJ. An incomplete program of cellular tyrosine phosphorylations induced by kinase-defective epidermal growth factor receptors. J Biol Chem 1995;270:12085-93.
33. Penar PL, Khoshyomn S, Bhushan A, Tritton TR. Inhibition of epidermal growth factor receptor associated tyrosine kinase blocks glioblastoma invasion of the brain. Neurosurgery 1997;40:141-51.
34. Curtis SW, Washburn T, Sewall C, et al. Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proc Natl Acad Sci U S A 1996;93:12626-30.
35. Coward L, Kirk M, Albin N, Barnes S. Analysis of plasma isoflavones by reversed-phase HPLC-multiple reaction ion monitoring-mass spectrometry. Clin Chim Acta 1996;247:121-42.
36. Constantinou A, Huberman E. Genistein, an inducer of tumor cell differentiation: possible mechanisms of action. Proc Soc Exp Biol Med 1995;208:109-15.
37. Jing Y, Waxman S. Structural requirements for differentiation-induction and growth-inhibition of mouse erythroleukemia cells by isoflavones. Anticancer Res 1995;15:1147-52.
38. Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett 1996; 110:41-8.
39. Shimokado K, Umezawa K, Ogata J. Tyrosine kinase inhibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells. Exp Cell Res 1995;220:266-73.
40. Kuzumaki T, Matsuda A, Ito K, Ishikawa K. Cell adhesion to substratum and activation of tyrosine kinases are essentially required for G1/S phase transition in BALB/c 3T3 fibroblasts. Biochem Biophys Acta 1996;1310:185-92.
41. Roberts AB, Flanders KC, Heine UI, et al. Transforming growth factor-beta: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci 1990;327:145-54.
42. Datto MB, Yu Y, Wang X-F. Functional analysis of the transcription factor beta responsive elements in the WAF/CIP1/p21 promoter. J Biol Chem 1995;270:28263-8.
43. Lawrence DA. Transforming growth factor-beta: a general review. Eur Cytokine Netw 1996;7:363-74.
44. Massague J, Weis-Garcia F. Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals. Cancer Surv 1996;27:41-64.
45. Peterson TG, Barnes S, Kim H. Genistein may inhibit the growth of human mammary epithelial (HME) cells by augmenting transforming growth factor beta (TGFβ) signaling. Am J Clin Nutr 1998;68:1527S-8S (abstr).
46. Danielpour D, Dart LL, Flanders KC, Roberts AB, Sporn MB. Immunodetection and quantification of the two forms of transforming growth factor[hyphen]β (TGFβ1 and TGFβ2) secreted by cells in culture. J Cell Physiol 1989;138:79-87.
47. Peterson TG, Coward L, Kirk M, Falany CN, Barnes S. The role of metabolism in mammary epithelial cell growth inhibition by the isoflavones genistein and biochanin A. Carcinogenesis 1996;17:1861-9.
48. Haitjema T, Westermann CJ, Overtoom TT, et al. Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): new insights in pathogenesis, complications, and treatment. Arch Intern Med 1996;156:714-9.
49. Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci U S A 1993;90:2690-4.
50. Fotsis T, Pepper M, Adlercreutz H, Hase T, Montesano R, Schweigerer L. Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J Nutr 1995; 125(suppl):790S-7S.
51. Korzenik JR, Barnes S, White RI Jr. Possible efficacy of isolated soy protein in treatment of hereditary hemorrhagic telangiectasia-associated epistaxis, gastrointestinal hemorrhage, and migraine: a pilot study. Am J Clin Nutr 1998;68:1530S (abstr).
52. McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGFβ-binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994;8:345-51.
53. Vincent P, Plauchu H, Hazan J, Faure S, Weissenbach J, Godet J. A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q. Hum Mol Genet 1995;4:945-9.
54. Johnson DW, Berg JN, Baldwin MA, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 1996;13:189-95.
55. McAllister KA, Baldwin MA, Thukkani AK, et al. Six novel mutations in the endoglin gene in hereditary hemorrhagic telangiectasia type 1 suggest a dominant-negative effect of receptor function. Hum Mol Genet 1995;4:1983-5.
56. Chen H, Tritton TR, Kenny N, Absher M, Chiu JF. Tamoxifen induces TGF-beta 1 activity and apoptosis of human MCF-7 breast cancer cells in vitro. J Cell Biochem 1996;61:9-17.
57. Charpentier A, Groves S, Simmons-Menchaca M, et al. RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells. Nutr Cancer 1993;19:225-39.
58. Arjmandi BH, Alekel L, Hollis B, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 1996;126:161-7.
59. Blair H, Jordan SE, Peterson TG, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J Cell Biochem 1996;61:629-37.
60. Linkhart TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair: IGF, TGF beta and BMP. Bone 1996;19(suppl):1S-12S.
61. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta. Nat Med 1996;2:1132-6.
62. Ikeda T, Shigeno C, Kasai R, et al. Ovariectomy decreases the mRNA levels of transforming growth factor-beta 1 and increases the mRNA levels of osteocalcin in rat bone in vivo. Biochem Biophys Res Commun 1993;194:1228-33.
63. Atfi A, Drobetsky E, Boissonneault M, Chapdelaie A, Chevalier S. Transforming growth factor β down-regulates src family protein tyrosine kinase signaling pathways. J Biol Chem 1994; 269:30688-93.
64. c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest 1992;90:1622-7.
65. Williams JP, Jordan SE, Barnes S, Blair HC. Tyrosine kinase inhibitor effects on osteoclastic acid transport. Am J Clin Nutr 1998;68:1369S-74S.
66. Cantley LC, Auger KR, Carpenter C, et al. Oncogenes and signal transduction. Cell 1991;64:281-302.
67. Lowenstein EJ, Daly RJ, Batzer AG, et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 1992;70:431-42.
68. Fotsis T, Zhang Y, Pepper MS, et al. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 1994;368:237-9.
69. Zhang L, Rees MC, Bicknell R. The isolation and long-term culture of normal human endometrial epithelium and stroma. Expression of mRNAs for angiogenic polypeptides basally and on oestrogen and progesterone challenges. J Cell Sci 1995;108:323-31.
70. Thomas KA. Vascular endothelial growth factor, a potent and selective angiogenic agent. J Biol Chem 1996;271:603-36.
71. Peterson TG, Ji G-P, Kirk M, Coward L, Falany CN, Barnes S. Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines. Am J Clin Nutr 1998;68:1505S-11S.
72. Meeker DR, Kesten HD. Effects of high protein diets on experimental atherosclerosis of rabbits. Arch Pathol 1941;31:147-62.
73. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995;333:276-82.
74. Anthony MS, Clarkson TB, Hughes CL Jr, Morgan TM, Burke GL. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 1996;126:43-50.
75. Honore EK, Williams JK, Anthony MS, Clarkson TB. Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques. Fertil Steril 1997;67:148-54.
76. Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. N Engl J Med 1991;325:756-62.
77. Grainger DJ, Kemp PR, Metcalfe JC, et al. The serum concentration of active transforming growth factor β is severely depressed in advanced atherosclerosis. Nat Med 1995;1:74-9.
78. Grainger DJ, Witchell CM, Metcalfe JC. Tamoxifen elevates transforming growth factor β and suppresses diet-induced formation of lipid lesions in mouse aorta. Nat Med 1995;1:1067-73.
79. Colletta AA, Benson JR, Baum M. Alternative mechanisms of action of anti-oestrogens. Breast Cancer Res Treat 1994;31:5-9.
80. Perry RR, Kang Y, Greaves BR. Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells. Br J Cancer 1995;72:1441-6.
81. Butta A, MacLennan K, Flanders KC, et al. Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res 1992;52:4261-4.
82. Miller JJS, Thompson JH, Zhang X-J, et al. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 1995;109:1475-83.
83. Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 1995;208:124-30.
84. Sadowska-Krowicka H, Mannick EE, Oliver PD, et al. Genistein and gut inflammation: role of nitric oxide. Proc Soc Exp Biol Med 1998;217:351-7.
85. Vodovotz Y, Geiser AG, Chesler L, et al. Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse. J Exp Med 1996;183:2337-42.
86. Chait A. Effects of isoflavones on LDL-cholesterol in vitro but not in vivo. Am J Clin Nutr 1998;68:15235 (abstr).
87. Wang W, Franke A, Custer LJ, Marchand LL. Antioxidant properties of dietary phenolic agents in a human LDL-oxidation ex vivo model. Am J Clin Nutr 1998;68:1523S (abstr).
88. Lee DC, Barlow KD, Gaido KW. The actions of 2,3,7,8-tetra-chlorodibenzo-p-dioxin on transforming growth factor-beta 2 promoter activity are localized to the TATA box binding region and controlled through a tyrosine kinase-dependent pathway. Toxicol Appl Pharmacol 1996;137:90-9.
89. Li JD, Dohrman AF, Gallup M, et al. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci U S A 1997;94:967-72.
90. Novogrodsky A, Vanichkin A, Patya M, Gazit A, Osherov N, Levitzki A. Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. Science 1994;264:1319-22.
91. Daly C, Reich NC. Double-stranded RNA activates novel factors that bind to the interferon-stimulated response element. Mol Cell Biol 1993;13:3756-64.
92. Baker ME. Evolution of regulation of steroid-mediated intercellular communication in vertebrates: insights from flavonoids, signals that mediate plant-rhizobia symbiosis. J Steroid Biochem Mol Biol 1992;41:301-8.
93. Korach KS, Couse JF, Curtis SW, et al. Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. Recent Prog Horm Res 1996;51:159-86.
94. Ogawa S, Lubahn DB, Korach KS, Pfaff DW. Aggressive behaviors of transgenic estrogen-receptor knockout male mice. Ann N Y Acad Sci 1996;794:384-5.
95. Eddy EM, Washburn TF, Bunch DO, et al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 1996;137:4796-805.
96. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes. A 26-year follow up of the Framingham population. Am Heart J 1986;113:383-90.
97. Ettinger B, Friedman GD, Bush T, Quesenberry CP Jr. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol 1996;87:6-12.
98. Tang MX, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996;348:429-32.
99. 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 U S A 1996;93:5925-30.
100. Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863-70.
101. Shughrue PJ, Komm B, Merchenthaler I. The distribution of estrogen receptor-beta mRNA in the rat hypothalamus. Steroids 1996;61:678-81.
102. Pink JJ, Fritsch M, Bilimoria MM, Assikis VJ, Jordan VC. Cloning and characterization of a 77-kDa oestrogen receptor isolated from a human breast cancer cell line. Br J Cancer 1997;75:17-27.