Anticancer Therapeutic Potential of Soy Isoflavone, Genistein

  • Mepur H. Ravindranath
  • Sakunthala Muthugounder
  • Naftali Presser
  • Subramanian Viswanathan
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 546)

Abstract

Genistein (4′5, 7-trihydroxyisoflavone) occurs as a glycoside (genistin) in the plant family Leguminosae, which includes the soybean (Glycine max). A significant correlation between the serum/plasma level of genistein and the incidence of gender-based cancers in Asian, European and American populations suggests that genistein may reduce the risk of tumor formation. Other evidence includes the mechanism of action of genistein in normal and cancer cells. Genistein inhibits protein tyrosine kinase (PTK), which is involved in phosphorylation of tyrosyl residues of membrane-bound receptors leading to signal transduction, and it inhibits topoisomerase II, which participates in DNA replication, transcription and repair. By blocking the activities of PTK, topoisomerase II and matrix metalloprotein (MMP9) and by down-regulating the expression of about 11 genes, including that of vascular endothelial growth factor (VEGF), genistein can arrest cell growth and proliferation, cell cycle at G2/M, invasion and angiogenesis. Furthermore, genistein can alter the expression of gangliosides and other carbohydrate antigens to facilitate their immune recognition. Genistein acts synergistically with drugs such as tamoxifen, cisplatin, 1,3bis 2-chloroethyl-1-nitrosourea (BCNU), dexamethasone, daunorubicin and tiazofurin, and with bioflavonoid food supplements such as quercetin, green-tea catechins and black-tea thearubigins. Genistein can augment the efficacy of radiation for breast and prostate carcinomas. Because it increases melanin production and tyrosinase activity, genistein can protect melanocytes of the skin of Caucasians from UV-B radiation-induced melanoma.

Keywords

Vascular Endothelial Growth Factor Breast Cancer Cell Prostate Cancer Cell Focal Adhesion Kinase Tyrosine Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Adlercreutz H., Markkanen H., and Watanabe S., 1993, Plasma concentrations of phyto-oestrogens in Japanese men, Lancet. 342:1209–1210.PubMedCrossRefGoogle Scholar
  2. Adelcreutz H., and Mazur W., 1997, Phytoestrogens and western diseases, Ann. Med. 29:95–120.Google Scholar
  3. Agarwal R., 2000, Cell Signaling and Regulators of Cell Cycle as Molecular Targets for Prostate Cancer Prevention by Dietary Agents, J Biochem Pharm. 60:1051–1059.CrossRefGoogle Scholar
  4. Ahmed N., Pansino F., Baker M., Rice G., and Quinn M., 2002, Association between alphavbeta6 integrin expression, elevated p42/44 kDa MAPK, and plasminogen-dependent matrix degradation in ovarian cancer, J Cell Biochem. 84:675–686.PubMedCrossRefGoogle Scholar
  5. Akaza H., Miyanaga N., Takashima N., Naito S., Hirao Y., Tsukamoto T., and Mori M., 2002. Is daidzein nonmetabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration, Jpn J Clin Oncol. 32:296–300.PubMedCrossRefGoogle Scholar
  6. Akiyama T., Ishida J., Nakagawa S., Ogawara H., Wantanabe S., Itoh N., Shibuya M., and Fukami Y., 1987, Genistein, a specific inhibitor of tyrosine-specific protein kinases, J Biol Chem. 262:5592–5595.PubMedGoogle Scholar
  7. Allred C.D., Allred K.F., Ju Y.H., Virant S.M., and Helferich W.G., 2001a, Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner, Cancer Res. 61:5045–5050.PubMedGoogle Scholar
  8. Allred C.D., Ju Y.H., Allred K.F., Chang J., and Helferich W.G., 2001b, Dietary genistein stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein, Carcinogenesis. 22:1667–1673.PubMedCrossRefGoogle Scholar
  9. Ando S., Nojima K., Majima H., Ishihara H., Suzuki M., Furusawa Y., Yamaguchi H., Koike S., Ando K., Yamauchi M., and Kuriyama T., 1998, Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line, Cancer Lett. 132:75–80.PubMedCrossRefGoogle Scholar
  10. Andrew D.P., Yoshino T., Guh L., Martin-Simonet M.T., and Butcher E.C., 1995, TABS, a T cell activation antigen that induces LFA-1-dependent aggregation, JImmunol. 155:1671–1684.Google Scholar
  11. Arai N., Strom A., Rafter J.J., and Gustafsson J.A., 2000, Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein, Biochem Biophys Res Commun. 270:425–431.PubMedCrossRefGoogle Scholar
  12. Arts J., Grimbergen J., Toet K., and Kooistra T., 1999, On the role of c-Jun in the induction of PAI-1 gene expression by phorbol ester, serum, and IL- 1 alpha in HepG2 cells, Anterioscler Thromb Vasc Biol. 19:39–46.CrossRefGoogle Scholar
  13. Bagnato A., Tecce R., Di Castro V., and Catt K.J., 1997, Activation of mitogenic signaling by endothelin 1 in ovarian carcinoma cells, Cancer Res. 57:1306–1311.PubMedGoogle Scholar
  14. Balabhadrapathruni S., Thomas T.J., Yurkow E.J., Amenta P.S., and Thomas T., 2000, Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells, Oncol Rep. 7:3–12.PubMedGoogle Scholar
  15. Barnes S., Peterson T., and Coward L., 1995, Rationale for the use of Genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer, J Cell Biochem Suppl. 22:181–187.PubMedCrossRefGoogle Scholar
  16. Barnes S., Sfakianos J., Coward L., and Kirk M., 1996, Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues, Adv Exp Med Biol. 401:87–100.PubMedCrossRefGoogle Scholar
  17. Belka C., Ahlers A., Sott C., Gaestel M., Herrmann F., and Brach M.A., 1995, Interleukin (IL)-6 signaling leads to phosphorylation of the small heat shock protein (Hsp) 27 through activation of the MAPKAP kinase 2 pathway in monocytes and monocytic leukemia cells, Leukemia. 9:288–294.PubMedGoogle Scholar
  18. Bergaamaschi G., Rosti V., Danova M., Ponchio L., Lucotti C., and Cazzola M., 1993, Inhibitors of tyrosine phosphorylation induce apoptosis in human leukemic cell lines, Leukemia. 7:2012–2018.Google Scholar
  19. Bergan R., Kyle E., Nguyen P., Trepel J., Ingui C., and Neckers L., 1996, Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin, Clin Exp Metastasis. 14:389–398.PubMedCrossRefGoogle Scholar
  20. Bhatia N., and Agarwal R., 2001, Detrimental effect of cancer preventive phytochemicals silymarin, Genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells, Prostate. 46:98–107.PubMedCrossRefGoogle Scholar
  21. Bishop J. M., 1983, Oncogenes and proto-oncogenes, Hosp Pract. 18:67–74.Google Scholar
  22. Boros L.G., B. S., Lim S., and Lee W.N., 2001, Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth, Pancreas. 22:1–7.PubMedCrossRefGoogle Scholar
  23. Borradaile N.M., de Dreu L.E., Wilcox L.J., Edwards J.Y., and Huff M.W., 2002, Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HebG2 cells through multiple mechanisms, Biochem J. 366:531–539.PubMedCrossRefGoogle Scholar
  24. Borsellino N., Bonavida B., Ciliberto G., Toniatti C., Travali S., and D’Alessandro N., 1999, Blocking signaling through the Gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity, Cancer. 85:134–144.PubMedCrossRefGoogle Scholar
  25. Bronte V., Macino B., Zambon A., Rosato A., Mandruzzato S., Zanovello P., and Collavo D., 1996, Protein tyrosine kinases and phosphatases control apoptosis induced by extracellular adenosine 5′ triphosphate, Biochem Biophys Res Commun. 218:344–351.PubMedCrossRefGoogle Scholar
  26. Burgener D., Bonjour J.P., and Caverzasio J. 1995, Fluoride increases tyrosine kinase activity in osteoblast-like cells: regulatory role for the stimulation of cell proliferation and Pi transport across the plasma membrane, J Bone Miner Res. 10:64–171.Google Scholar
  27. Cafferata E.G., Gonzalez-Guerrico A.M., Giordano L., Pivetta O.H., and Santa-Coloma T.A., 2000, Interleukin1beta regulates CFTR expression in human intestinal T84 cells, Biochim Biophys Acta. 1500:241–248.PubMedCrossRefGoogle Scholar
  28. Cappelletti V., Fioravanti L., Miodini P., and Di Fronzo G., 2000, Genistein blocks breast cancer cells in the G (2) M phase of the cell cycle, J Cell Biochem. 79:594–600.PubMedCrossRefGoogle Scholar
  29. Carlo-Stella C., Dotti G., Mangoni L., Regazzi E., Garau D., Bonati A., Almici C., Sammarelli G., Savoldo B., Rizzo M.T., and Rizzoli V., 1996a, Selection of myeloid progenitors lacking BCR/ABL mRNA in chronic myelogenous leukemia patients after in vitro treatment with the tyrosine kinase inhibitor genistein, Blood. 88:3091–3100.PubMedGoogle Scholar
  30. Carlo-Stella C., Regazzi E., Garau D., Mangoni L., Rizzo M.T., Bonati A., Dotti G., Almici C., and Rizzoli V., 1996b, Effect of the protein tyrosine kinase inhitibor genistein on normal leukaemic haemopoietic progenitor cells, Br J Haematol. 93:551–557.PubMedCrossRefGoogle Scholar
  31. Casagrande F., Darbon J.M., 2000, P21 CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells, J Exp Cell Res. 258:101–108.CrossRefGoogle Scholar
  32. Cataldi M., Taglialatela M., Guerriero S., Amoroso S., Lombardi G., di Renzo G., and Annunziato L., 1996, Protein-tyrosine kinases activate while protein-tyrosine phosphatases inhibit L-type calcium channel activity in pituitary GH3 cells, J Biol Chem. 19:9441–9446.Google Scholar
  33. Cattaneo M.G., D’atri F., and Vicentini L.M., 1997, Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells, Biochem J. 328:499–503.PubMedGoogle Scholar
  34. Chen C.L., Levin A., Rao A., O’Neill K., Mess Inger Y., Myers D.E., Goldman F., Hurvitz C., Casper J.T., and Uckun F.M., 1999, Clinical pharmacokinetics of the CD 19 receptors-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies, J Clin Pharmacol. 39:1248–1255.PubMedCrossRefGoogle Scholar
  35. Chen X., Anderson J.J., 2001, Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway, N.utr Cancer. 41:165–171.Google Scholar
  36. Choi Y.H., Lee W., Park K.Y., and Zhang L., 2000, 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. 91:164–173.PubMedCrossRefGoogle Scholar
  37. Choi Y.H., Zhang L., Lee W.H., and Park K.Y., 1998, Genistein-induced G2/M arrest is associated with the inhibition of cyclin B1 and the induction of p21 in human breast carcinoma cells, Int J Oncol 13:391–396.PubMedGoogle Scholar
  38. Clark J.W., Santos-Moore A., Stevenson L.E., and Frackelton A.R. Jr., 1996, 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 65:186–191.PubMedCrossRefGoogle Scholar
  39. Constantinou A. and Huberman E., 1995, Genistein as an inducer of tumor cell differentiation: possible mechanisms of action. Proc Soc Exp Biol Med. 208:109–15.PubMedGoogle Scholar
  40. Constantinou A., Kiguchi K., and Huberman E., 1990, Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res. 50:2618–2624.PubMedGoogle Scholar
  41. Constantinou A.I., Kamath N., and Murley J.S., 1998a, Genistein inactivates bc1–2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells, Eur J Cancer. 34:1927–1934.PubMedCrossRefGoogle Scholar
  42. Constantinou A.I., Krygier A.E., and Mehta R.R., 1998b, Genistein induces maturation of cultured human breast cancer cells and prevents tumor growth in nude mice, Am J Clin Nutr. 68:1426S-1430S.Google Scholar
  43. Cruz M.L., Wong W.W., Mimouni F., Hachey D.L., Setchell K.D., Klein P.D., and Tsang R.C., 1994, Effects of infant nutrition on cholesterol synthesis rates, Pediatr Res. 35:135–140.PubMedCrossRefGoogle Scholar
  44. Dampier K., Hudson E.A., Howells L.M., Manson M.M., Walker R.A., and Gescher A., 2001, Differences between human breast cell lines in susceptibility towards growth inhibition by genistein, Br J Cancer. 85:618–624.PubMedCrossRefGoogle Scholar
  45. Darbon J.M., Penary M., Escalas N., Casagrande F., Goubin-Gramatica F., Baudouin C., and Ducommun B., 2000, Distinct Chk2 Activation Pathways Are Triggered by Genistein and DNA-damaging Agents in Human Melanoma Cells, J Biol Chem. 275:15363–15369.PubMedCrossRefGoogle Scholar
  46. Das R., and Vonderhaar B.K., 1996, Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells, Breast Cancer Res Treat 40:141–149.PubMedCrossRefGoogle Scholar
  47. Davis J.N., Kucuk O., and Sarkar F.H., 2002, Expression of prostate-specific antigen is transcriptionally regulated by Genistein in prostate cancer cells, Mol Carcinog. 34:91–101.PubMedCrossRefGoogle Scholar
  48. Davis J.N., Kucuk O., Djuric Z., and Sarkar F.H., 2001, Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes., Free Radic Biol Med, 30:1293–1302.PubMedCrossRefGoogle Scholar
  49. Davis J.N., Kucuk, O., and Sarkar F.H., 1999, Genistein inhibits NF-kappa B activation in prostate cancer cells, Nutr Cancer. 35:167–174.PubMedCrossRefGoogle Scholar
  50. Davis J.N., Muqim N., Bhuiyan M., Kucuk O., Pienta KJ, and Sarkar F.H., 2000, Inhibition of prostate specific antigen expression by Genistein in prostate cancer cells, Int J Oncol. 16:1091–1097.PubMedGoogle Scholar
  51. de la Taille A., Katz A., Vacherot F., Saint F., Salomon L., Cicco A., Abbou C.C., and Chopin D.K., 2001, Cancer of the prostate: influence of nutritional factors. A new nutritional approach, Presse Med. 30:561–564.PubMedGoogle Scholar
  52. den Tonkelaar I, Keinan-Boker L, Veer PV, Arts CJ, Adlercreutz H, Thijssen JH, Peeters PH. 2001. Urinary phytoestrogens and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prey. 10:223–228.Google Scholar
  53. Deora A.B., Miranda M.B., and Rao S.G., 1997, Down-modulation of P210bcr/abl induces apoptosis/differentiation in K562 leukemic blast cells, Tumori. 83:756–761.PubMedGoogle Scholar
  54. Diel P., Olff S., Schmidt S., and Michna H., 2001, Molecular identification of potential selective estrogen receptor modulator (SERM) like properties of phytoestrogens in the human breast cancer cell line MCF-7, Planta Med. 67:510–514.PubMedCrossRefGoogle Scholar
  55. Ding D.X., Rivas C.I., Heaney M.L., Raines M.A., Vera J.C., and Golde D.W., 1994, The alpha subunit of the human granulocyte-macrophage colony-stimulating factor receptor signals for glucose transport via a phosphorylation-independent pathway, Proc Natl Acad Sci USA. 91:2537–2541.PubMedCrossRefGoogle Scholar
  56. Ding X.Z., Tong W.G., and Adrian T.E., 2001, 12-lipoxygenase metabolite 12(S)-HETE stimulates human pancreatic cancer cell proliferation via protein tyrosine phosphorylation and ERK activation, Int J Cancer. 94:630–636.PubMedCrossRefGoogle Scholar
  57. Elatter T.M., Virji A.S., 2000, The inhibitory effect of curcumin, Genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro, Anticancer Res. 20:1733–1738.Google Scholar
  58. El-Zarruk A.A., and van den Berg H.W., 1999, The anti-proliferative effects of tyrosine kinase inhibitors towards tamoxifen-sensitive and tamoxifen-resistant human breast cancer cell lines in relation to the expression of epidermal growth factor receptors (EGF-R) and the inhibition of EGF-R tyrosine kinase, Cancer Lett. 142:185–193.PubMedCrossRefGoogle Scholar
  59. Ek O., Yanishevski Y., Zeren T., Waurzyniak B., Gunther R., Chelstrom L., Chandan-Langlie M., Schneider E., Myers D.E., Evans W., and Uckun F.M., 1998, In vivo toxicity and pharmacokinetic features of B43 (Anti-CD19)- Genistein immunoconjugate, Leuk Lymphoma. 30:389–394.PubMedGoogle Scholar
  60. Farhan H., Wahala K., Adlercreutz H., and Cross H.S., 2002, Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells., J Chromatogr B Analyt Technol. Biomed Life Sci. 777:261–268.PubMedCrossRefGoogle Scholar
  61. Finlay G.J., Holaway K.M., and Baguley B.C., 1994, Comparison of the effects of genistein and amsacrine on leukemia cell proliferation, Oncol Res. 6:33–37.PubMedGoogle Scholar
  62. Fioravanti L., Cappelletti V., Miodini P., Ronchi E., Brivio M., and Di Fronzo G., 1998, Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro. Cancer Lett. 130:143–152.PubMedCrossRefGoogle Scholar
  63. Fiorelli G., Picariello L., Martineti V., Tonelli F., and Brandi M.L., 1999, Estrogen synthesis in human colon cancer epithelial cells, J Steroid Biochem Mol Biol. 71:223–230.PubMedCrossRefGoogle Scholar
  64. Frey R.S., and Singletary K.W., 2003, Genistein activates p38 mitogen-activated protein kinase, inactivates ERK1/ERK2 and decreases Cdc25c expression in immortalized human mammary epithelial cells, J Nutr. 133:226–231.PubMedGoogle Scholar
  65. Frey R.S., Li J., and Singletary K.W., 2001, Effects of genistein on cell proliferation and cell cycle arrest in nonneoplastic human mammary epithelial cells: involvement of Cdc2, p21 (waf/cip 1), p27 (kipl), and Cdc25c expression, Biochen Pharmacol. 61:979–989.CrossRefGoogle Scholar
  66. Fujimoto N., Sueoka N., Sueoka E., Okabe S., Suganuma M., Harada M., and Fujiki H., 2002, Lung cancer prevention with (-)-epigallocatechin gallate using monitoring by heterogenous nuclear ribonucleoprotein B 1, Int J Oncol. 20:1233–1239.PubMedGoogle Scholar
  67. Geller J., Sionit L., Partido C., Li L., Tan X., Youngkin T., Nachtsheim D., and Hoffman R.M., 1998, Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture, Prostate. 34:75–79.PubMedCrossRefGoogle Scholar
  68. Ghafar M.A., Golliday E., Bingham J., Mansukhani M.M, Anastasiadis A.G., and Katz A.E., 2002, Regression of prostate cancer following administration of Genistein Combined Polysaccharide (GCP), a nutritional supplement: a case report, J Altern Complement Med. 8:493–497.PubMedCrossRefGoogle Scholar
  69. Grandaliano G., Monno R., Ranieri E., Gesualdo L., Schena F.P., Martino C., and Ursi M, 2000, Regenerative and proinflammatory effects of thrombin on human proximal tubular cells, JAm Soc Nephrol. 11:1016–1025.Google Scholar
  70. Guo Q., Rimbach G., Moini H., Weber S., and Packer L., 2002, ESR and cell culture studies on free radicalscavenging and antioxidant activities of isoflavonoids, J Toxicology. 179:171–180.CrossRefGoogle Scholar
  71. Hagmann W., 1994, Cell proliferation status, cytokine action and protein tyrosine phosphorylation modulate leukotriene biosynthesis in a basophil leukaemia and a mastocytoma cell line, Biochem J. 299:467–472.PubMedGoogle Scholar
  72. Hartman R.R., Rimoldi D., Lejeune F.J., and Carrel S., 1997, Cell differentiation and cell-cycle alterations by tyrosine kinase inhibitors in human melanoma cells, Melanoma Res. 7:S27–S33.CrossRefGoogle Scholar
  73. Heruth D.P., Wetmore L.A., Leyva A., and Rothberg P.G., 1995, Influence of protein tyrosine phosphorylation on the expression of the c-myc oncogene in cancer of the large bowel, J Cell Biochem. 58:83–94.PubMedCrossRefGoogle Scholar
  74. Hedlund T.E., Johannes W.U., Miller G.J., 2003, Soy isoflavonoid equol modulates the growth of benign and malignant prostatic spithelial cells in vitro, J Prostate. 54:68–78.CrossRefGoogle Scholar
  75. Hillman G.G., Forman J., Kucuk O., Yudelev M., Maughan R.L., Rubio J., Layer A., Tekyi-Mensah S., Abrams J., and Sarkar F.H., 2001, Genistein potentiates the radiation effect on prostate carcinoma cells, Clin Cancer Res. 7:382–390.PubMedGoogle Scholar
  76. Hoffman R., 1995, Potent inhibition of breast cancer cell lines by the isoflavonoid kievitone: comparison with genistein, Biochem Biophys Res Commun. 211:600–606.PubMedCrossRefGoogle Scholar
  77. Honke K., Tsuda M., Hirahara Y., Miyao N., Tsukamoto T., Satoh M., and Wada Y, 1998, Cancer-associated expression of glycolipid sulfotransferase gene in human renal cell carcinoma cells, Cancer Res. 58:3800–3805.PubMedGoogle Scholar
  78. Honma Y., Okabe-Kado J., Kasukabe T., Hozumi M., and Umezawa K., 1990, Inhibition of ab 1 oncogene tyrosine kinase induces differentiation of human myelogenous leukemia K562 cells. Jpn J Cancer Res. 81:1132–113.PubMedCrossRefGoogle Scholar
  79. Hooijberg J.H., Broxterman H.J., Heijn M., Fles D.L., Lankelma J., and Pinedo H.M., 1997, Modulation by (iso) flavonoids of the ATPase activity of the multidrug resistance protein, FEBS Lett. 413:344–348.PubMedCrossRefGoogle Scholar
  80. Hsieh C.Y., Santell R.C., Haslam S.Z., and Helferich W.G., 1998, Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo, Cancer Res. 58:3833–3838.PubMedGoogle Scholar
  81. Hu Y., Dragowska W.H., Wallis A., Duronio V., and Mayer L., 2001, Cytotoxicity induced by manipulation of signal transduction pathways is associated with down-regulation of Bc1–2 but not Mc1–1 in MCF-7 human breast cancer, Breast Cancer Res Treat. 70:11–20.PubMedCrossRefGoogle Scholar
  82. Hunakova L., Sedlak J., Klobusicka M., Duraj J., and Chorvath B., 1994, Tyrosine kinase inhibitor-induced differentiation of D-562 cells: alterations of cell cycle and cell surface phenotype, Cancer Lett. 81:81–87.PubMedCrossRefGoogle Scholar
  83. Ihn H., and Tamaki K., 2002, Mitogenic activity of dermatofibrosarcoma protuberas is mediated via an extracellular signal related kinase dependent pathway, J Invest Dermatol. 119:954–960.PubMedCrossRefGoogle Scholar
  84. Iida J., Meijne A.M., Spiro R.C., Roos E., Furct L.T., and McCarthy J.B., 1995, Spreading and focal contact formation of human melanoma cells in response to the stimulation of both melanoma-associated proteoglycan (NG2) and alpha 4 beta 1 integrin, Cancer Res. 55:2177–2185.PubMedGoogle Scholar
  85. Jenab S., Morris P.L., 1997, Transcriptional regulation of Sertoli cell immediate early genes by interleukin-6 and interferon-gamma is mediated through phosphorylation of STAT 3 and STAT 1 proteins, Endocrinology 138:2740–2746.PubMedCrossRefGoogle Scholar
  86. Jones T.H., Justice S.K., and Price A., 1997, Suppression of tyrosine kinase activity inhibits [3H] thymidine uptake in cultured human pituitary tumor cells, J Clin Endocrinol Metab. 82:2143–2147.PubMedCrossRefGoogle Scholar
  87. Ju Y.H., Allred C.D., Allred K.F., Karko K.L., Doerge D.R., and Helferich W.G., 2001, Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice, J Nutr. 131:2957–2962.PubMedGoogle Scholar
  88. Ju Y.H., Doerge D.R., Allred K.F., Allred C.D., and Helferich W.G., 2002, Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice, Cancer Res. 62:2474–2477.PubMedGoogle Scholar
  89. Katdare M., Osborne M., Telang N.T., 2002, Soy isoflavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene expressing human breast epithelial cells. Int J Oncol. 21:809–815.PubMedGoogle Scholar
  90. Katdare M., Osborne M.P., and Telang N.T., 1998, Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals, Oncol Rep 5:311–315.PubMedGoogle Scholar
  91. Kawase T., Oriskasa M., Oguro A., and Burns DM., 1999, Possible regulation of epidermal growth factor-receptor tyrosine autophosphorylation by calcium and G proteins in chemically permeabilized rat UMR106 cells, Arch Oral Biol. 44:157–171.PubMedCrossRefGoogle Scholar
  92. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., and Reeder A.Y., 1993, Metabolites of dietary (soya) isoflavones in human urine, Clin Chim Acta. 223:9–22.PubMedCrossRefGoogle Scholar
  93. Khoshyomn S., Manske G.C., Lew S.M., Wald S.L., and Penar P.L., 2000. Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells, Pediatr Neurosurg. 33:123–131.PubMedCrossRefGoogle Scholar
  94. Khoshyomn S., Nathan D., Manske G.C., Osler T.M., and Penar P.L., 2002, Synergistic effect of genistein and BCNU on growth inhibition and cytotoxicity of glioblastoma cells, J Neurooncol. 57:193–200.PubMedCrossRefGoogle Scholar
  95. Kiguchi K., Constantinou A.I., and Huberman E., 1990, Genistein-induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells, Cancer Commun. 2:271–277.PubMedGoogle Scholar
  96. Kikuchi H., and Hossain A., 1999, Signal transduction-mediated CYPIA1 induction by omeprazole in human HepG2 cells., Exp Toxicol pathol. 51:342–346.PubMedCrossRefGoogle Scholar
  97. Kikuchi Y., and Nash H.A., 1979. Nicking-closing activity associated with bacteriophage lambda int gene product, Proc Natl Acad Sci USA. 76:3760–3764.PubMedCrossRefGoogle Scholar
  98. Kim J.G., Shin I., Lee K.S., and Han J.S., 2001, D609-sensitive tyrosine phosphorylation is involved in Fasmediated phospholipase, Exp Mol Med. 33:303–309.PubMedCrossRefGoogle Scholar
  99. Klein J.M., and McCarthy T.A., 1997, Inhibition of tyrosine kinase activity decreases expression of surfactant protein A in a human lung adenocarcinoma cell line independent of epidermal growth factor receptor, Biochim Biophys Acta. 1355:218–230.PubMedCrossRefGoogle Scholar
  100. Kobayashi T., Nakata T., and Kuzumaki T., 2002, Effect of flavonoids on cell cycle progression in prostate cancer cells, Cancer Lett. 176:17–23.PubMedCrossRefGoogle Scholar
  101. Kumar NB., Cantor A., Allen K., Ricardi D., and Cox C.E., 2002, The specific role of isoflavones on estrogen metabolism in premenopausal women, Cancer. 94:1166–1174.PubMedCrossRefGoogle Scholar
  102. Kumi-Diaka J., and Butler A., 2000, Caspase-3 protease activation during the process of genistein-induced apoptosis in TM4 testicular cells, Biol Cell. 92:115–124.PubMedCrossRefGoogle Scholar
  103. Kumi-Diaka J., Nguyen V., and Butler A., 1999, Cytotoxic potential of the phytochemical genistein isoflavone (4′, 5′, 7-trihydroxyisoflavone) and certain environmental chemical compounds on testicular cells, Biol Cell. 91:515–523.PubMedCrossRefGoogle Scholar
  104. Kumi-Diaka J., Rodriguez R., and Goudaze G., 1998, Influence of genistein (4′, 5′ 7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines, Biol Cell. 90:349–354.PubMedGoogle Scholar
  105. Kumi-Diaka J., Sanderson N., and Hall A., 2000, The mediating role of caspase-3 protease in the intracellular mechanism of Genistein-induced apoptosis in human prostatic carcinoma cell lines, DU 145 and LNCaP, Biol Cell. 92:594–604.Google Scholar
  106. Kuo M.L., Huang T.S., and Lin J.K., 1995, Preferential requirement for protein tyrosine phosphatase activity in the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of human colon cancer cells, Biochem Pharmacol. 50:1217–1222.PubMedCrossRefGoogle Scholar
  107. Kuo S.M., 1996, Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells, Cancer Lett. 110:41–48.PubMedCrossRefGoogle Scholar
  108. Kuo S.M., Morehouse H.F., and Lin C.P., 1997, Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells, Cancer Lett. 116:131–137.PubMedCrossRefGoogle Scholar
  109. Kuriu A., Ikeda H., Kanakura Y., Griffin J.D., Druker B., Yagura H., Kitayama H., Ishikawa J., Nichiura T., and Kanayama Y, et al., 1991, Proliferation of human myeloid leukemia cell line associated with the tyrosinephosphorylation and activation of the proto-oncogene c-kit product. Blood. 78:2834–2840.PubMedGoogle Scholar
  110. Kusaka M., and Sperelakis N., 1996, Genistein inhibition of fast Na+ current in uterine leiomyosarcoma cells is independent of tyrosine kinase inhibition, Biochim Biophys Acta. 1278:1–4.PubMedCrossRefGoogle Scholar
  111. Kyle E, Neckers L., Takimoto C., Curt G., and Bergan R., 1997, Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity, Mol Pharmacol. 51:193–200.PubMedGoogle Scholar
  112. Lamon-Fava S., 2000, Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line Hep G2, J. Nutr. 130:2489–2492.PubMedGoogle Scholar
  113. Lampe J.W., 2003, Isoflavonoid and lignan phytoestrogens as dietary biomarkers, J Nutr. 133:956S–964S.Google Scholar
  114. Lebakken C.S., McQuade K.J., and Rapraeger A.C., 2000, Syndecan1 signals independently of betal integrin s during Raji cell spreading, Exp Cell Res. 259:315–325.PubMedCrossRefGoogle Scholar
  115. Lei W., Mayotte J.E., and Levitt M.L., 1998, EGF-dependent and independent programmed cell death pathways in NCI-H596 normal cell lung cancer cells, Biochem Biophys Res Commun. 245:939–945.PubMedCrossRefGoogle Scholar
  116. Lei W., Mayotte J.E., and Levitt M.L., 1999, Enhancement of chemosensitivity and programmed cell death by tyrosine kinase inhibitors corelates with EGFR expression in non-small cell lung cancer cells, Anticancer Res. 19:221–228.PubMedGoogle Scholar
  117. Leung L.K., and Wang T.T., 2000, Bcl-2 is not reduced in the death of MCF-7 cells at low genistein concentration, J Nutr. 130:2922–2926.PubMedGoogle Scholar
  118. Leyton J., Garcia-Marin L.J., Tapia J.A., Jensen R.T., and Moody T.W., 2001, Bombesin and gastrin releasing peptide increase tyrosine phosphorylation of focal adhesion kinase and paxillin in non-smell cell lung cancer cells, Cancer Lett. 162:87–95.PubMedCrossRefGoogle Scholar
  119. Li W., and Weber G., 1998a, Synergistic action of tiazofurin and Genistein in human ovarian carcinoma cells, Oncol Res. 10:117–122.PubMedGoogle Scholar
  120. Li W., and Weber G., 1998b, Synergistic action of tiazofurin and genistein on growth inhibition and differentiation of K-562 human leukemic cells, Life Sci. 63:1975–1981.PubMedCrossRefGoogle Scholar
  121. Li Y., and Sarkar F., 2002a, Inhibition of nuclear factor kappaB activation in PC3 cells by Genistein is mediated via Akt signaling pathway, J Clin Cancer Res. 8:2369–2377.Google Scholar
  122. Li Y., and Sarkar F., 2002c, Gene expression profiles of Genistein-treated PC3 prostate cancer cells, J Nutr. 132:3623–3631.PubMedGoogle Scholar
  123. Li Y., and Sarkar F.H., 2002b, Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with Genistein, J Cancer Lett. 186:157–164.CrossRefGoogle Scholar
  124. Li Y., Bhuiyan M., Sarkar F.H., 1999b. Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. Int J Oncol. 15:525–533.PubMedGoogle Scholar
  125. Li Y., Upadhyay S., Bhuiyan M., and Sarkar F.H., 1999a, Induction of apoptosis in breast cancer cells MDAMB-231 by genistein, Oncogene. 18:3166–3172.PubMedCrossRefGoogle Scholar
  126. Lian F., Bhuiyan M., Li Y.W., Wall N., Kraut M., and Sarkar F.H., 1998, Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line, Nutr Cancer. 31:184–191.PubMedCrossRefGoogle Scholar
  127. Lian F., Li Y., Bhuiyan M., and Sarkar F.H., 1999, p53 independent apoptosis induced by genistein in lung cancer cells, Nutr Cancer. 33:125–131.PubMedCrossRefGoogle Scholar
  128. Liu Y., Bhalla K., Hill C., and Priest D.G., 1994, Evidence for involvement of tyrosine phosphorylation in taxolinduced apoptosis in a human ovarian tumor cell line, Biochem Pharmacol. 48:1265–1272.PubMedCrossRefGoogle Scholar
  129. Loukovaara M., Carson M., Palotie A., and Adlercreutz H., 1995, Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures, Steroids. 60:656–661.PubMedCrossRefGoogle Scholar
  130. Lu L.J., and Anderson K.E., 1998. Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans, Am J Clin Nutr. 68:1500S-1504S.Google Scholar
  131. Lu L.J., Anderson K.E., Grady J.J., Kohen F., and Nagamani M., 2000, Decreased ovarian hormones during a soya diet: implications for breast cancer prevention, Cancer Res. 60:4112–4121.PubMedGoogle Scholar
  132. Lu L.J., Bromeling L.D., Marshall M.V., and Ramanujam V.M., 1995, A simplified method to quantify isoflavones in commercial soybean diets and human urine after legume consumption, Cancer Epidemiol Biomarkers Prey. 4:497–503.Google Scholar
  133. Lu L.J., Lin S.N., Grady J.J., Nagamani M., and Anderson K.E., 1996, Altered kinetics and extent of urinary daidzein and genistein excretion in women during chronic soya exposure, Nutr Cancer. 26: 289–302.PubMedCrossRefGoogle Scholar
  134. Maeno T., Tanaka T., Sando Y., Suga T., Maeno Y., Nakagawa J., Hosono T., Sato M., Akiyama H., Kishi S., Nagai R., and Kurabayashi M., 2002, Stimulation of vascular endothelial growth factor gene transcription by all trans retinoic acid through Sp1 and Sp3 sites in human bronchioloalveolar carcinoma cells, Am J Respir Cell Mol Biol. 26:246–253.PubMedCrossRefGoogle Scholar
  135. Maggiolini M., Bonofiglio D., Marsico S., Panno M.L., Cenni B., Picard D., Ando S., 2001. Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol. 60:595:602.Google Scholar
  136. Maggiolini M., Vivacqua A., Carpino A., Bonofiglio D., Fasanella G., Salerno M., Picard D., and Ando S., 2002, The mutant androgen receptor T877A mediates the proliferative but not the cytotoxic dose-dependent effects of Genistein and quercetin on human LNCaP prostate cancer cells, Mol Pharmacol. 62:1027–1035.PubMedCrossRefGoogle Scholar
  137. Makishima M., Honma Y., Hozumi M., Sampi K., Hattori M., Umezawa K., Motoyoshi K., 1991, Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells. Leuk Res. 5:701:708.Google Scholar
  138. Marino M., Pallottini V., and Trentalance A., 1998, Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEP2 cells., Biochem Biophys Res Commun. 245:254–258.PubMedCrossRefGoogle Scholar
  139. Markiewicz L., Garey J., Adlercreutz H., and Gurpide E., 1993, In vitro bioassays of non-steroidal phytoestrogens, J Steroid Biochem Mol Biol. 45:399–405.PubMedCrossRefGoogle Scholar
  140. Markovits J., Pommier Y., Mattern M.R., Esnault C., Roques B.P., Le Pecq JB., and Kohn K.W., 1986. Effects of the bifunctional antitumor intercalator ditercalinium on DNA in mouse leukemia L1210 cells and DNA topoisomerase II, Cancer Res. 46:5821–5826.PubMedGoogle Scholar
  141. Mazur W., 1998, Phytoestrogen content in foods, Baillieres Clin Endocrinol Metab. 2:729–742Google Scholar
  142. Mazur W., and Adlecreut H., 2000, Overview of naturally occuring endocrine-active substances in the human diet in relation to human health, Nutrition. 16:654–658.PubMedCrossRefGoogle Scholar
  143. McMichael-Phillips D.F., Harding C., Morton M., Roberts S.A., Howell A., Potten C.S., and Bundred N.J., 1998, Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast, Am J Clin Nutr. 68:1431S-1435S.Google Scholar
  144. Messina M.J., and Loprinzi C.L., 2001, Soy for breast cancer survivors: a critical review of the literature, J Nutr. 131:3095S-3108S.Google Scholar
  145. Milovic V., Deubner C., Zeuzem S., Piiper A., Caspary W.F., and Stein J., 1995, EGF stimulates polyamine uptake in Caco-2 cells, Biochem Biophys Res Commun. 206:962–968.PubMedCrossRefGoogle Scholar
  146. Miodini P., Fioravanti L., Di Fronzo G., and Cappelletti V., 1999. The two phyto-oestrogens genistein and quercetin exert different effects on estrogen receptor function, Br J Cancer. 80:1150–1155.PubMedCrossRefGoogle Scholar
  147. Mitchell J.H., Cawood E., Kinniburgh D., Provan A., Collins A.R., and Irvine D.S., 2001, Effect of phytoestrogen food supplement on reproductive health in normal males, Clin Sci. 100:613–618.PubMedCrossRefGoogle Scholar
  148. Mitchell J.H., Duthie S., and Collins A.R., 2000, Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP, J Nutr Cancer. 38:223–228.CrossRefGoogle Scholar
  149. Mitropoulou T.N., Tzanakakis G.N., Nikitovic D., Tsatsakis A., and Karamanos N.K., 2002, In vitro effects of genistein on the synthesis and distribution of glycosaminoglycans/proteoglycans by estrogen receptor-positive and negative human breast cancer epithelial cells, Anticancer Res. 22:2841–2846.PubMedGoogle Scholar
  150. Monti E., and Sinha B.K., 1994, Antiproliferative effect of genistein and adriamycin against estrogen-dependent and independent human breast carcinoma cell lines, Anticancer Res. 14:1221–1226.PubMedGoogle Scholar
  151. Morisset J., Douziech N., Rydzewska G., Buscail L., and Rivard N., 1995, Cell signalling pathway involved in PACAP-induced AR4–2J cell proliferation, Cell Signal. 7:195–205.PubMedCrossRefGoogle Scholar
  152. Morton D.L., Ravindranath M.H., Irie R.F., 1994. Tumor gangliosides as targets for active specific immunotherapy of melanoma in man. Prog Brain Res. 101:251–275.PubMedCrossRefGoogle Scholar
  153. Morton M.S., Arisaka O., Miyake N., Morgan L.D., and Evans B.A., 2002, Phytoestrogen concentrations in serum from Japanese men and women over forty years of age, J Nutr. 132:3168–3171.PubMedGoogle Scholar
  154. Mousavi Y., Adlercreutz H., 1993, Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture, Steroids. 58:301–304.PubMedCrossRefGoogle Scholar
  155. Mukhopadhyay D., Tsiokas L., and Sukhatme V.P., 1998, High cell density induces vascular endothelial growth factor expression via protein tyrosine phosphorylation, Gene Expr. 7:53–60.PubMedGoogle Scholar
  156. Munoz R., Klingenberg O., Wiedlocha A., Rapak A., Falnes PO., and Olsnes S., 1997, Effect of mutation of cytoplasmic receptor domain and of Genistein on transport of acidic fibroblast growth factor into cells, On cogene. 15:525–536.Google Scholar
  157. Murkies A., Dalais F.S., Briganti E.M., Burger H.G., Healy D.L., Wahlqvist M.L., and Davis S.R., 2000. Phytoestrogens and breast cancer in postmenopausal women: a case control study, Menapause. 7:289–296.CrossRefGoogle Scholar
  158. Myers D.E., Jun X., Waddick K.G., Forsyth C., C helstrom L.M., Gunther R.L., Tumer N.E., Bolen J., and Uckun F.M., 1995. Membrane-associated CD19 LYN complex is an endogenous p53-independent and Bcl-2-independent regulator of apoptosis in human B-lineage lymphoma cells, Proc Nall Acad Sci USA. 92:9575–9579.CrossRefGoogle Scholar
  159. Myers D.E., Sicheneder A., Clementson D., Dvo rak N., Venkatachalam T., Sev A.R., Chandan-Langlie M., and Uckun F.M., 1998, Large scale manufacturing of B43 (anti-CD19)-genistein for clinical trials in leukemia lymphoma, Leuk Lymphoma. 29:329–338.PubMedCrossRefGoogle Scholar
  160. Naik H.R., Lehr J., and Pienta K.J., 1994, An in vitro and in vivo study of antitumor effects of Genistein on hormone refractory prostate cancer, Anticancer Res. 14:2617–2619.PubMedGoogle Scholar
  161. Nakagawa H., Yamamoto D., Kiyozuka Y., Tsuta K., Uemura Y., Hioki K., Tsutsui Y., and Tsubura A., 2000. Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines, J Cancer Res Clin Oncol. 126:448–454.PubMedCrossRefGoogle Scholar
  162. Nakanishi K., Fujimoto J., Ueki T., Kishimoto K., Hashimoto-Tamaoki T., Furuyama J., Itoh T., Saski Y., and Okamoto E., 1999, Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase, Clin Exp. Metastasis. 17:507–514.PubMedCrossRefGoogle Scholar
  163. Nomoto S., Arao Y., Horiguchi H., Ikeda K., Kayama F., 2002. Oestrogen causes G2/M arrest and apoptosis in breast cancer cells MDA-MB-231. Oncol Rep. 9:773–776.PubMedGoogle Scholar
  164. Oelmann E., Sreter L., Schuller I., Serve H., Koenigsmann M., Wiedenmann B., Oberberg D., Reufi B., Thiel E., and Berdel W.E., 1995, Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling, Cancer Res. 55:2212–2219.PubMedGoogle Scholar
  165. Ohno T., Kato N., Ishii E., Shimizu M., Ito Y., Tomono S., and Kawazu S., 1993, Genistein augments cyclic adenosine 3′5′-monophosphate (cAMP) accumulation and insulin release in MIN6 cells, Endocr Res. 19:273–285.PubMedCrossRefGoogle Scholar
  166. Okura A., Arakawa H., Oka H., Yoshinari T., and Monden Y., 1988. Effect of genistein on topoisomerase activity and on the growth of [Val 12] Ha-rastransformed NIH 3T3 cells, Biochem Biophys Res Commun. 157:183–189.PubMedCrossRefGoogle Scholar
  167. Onozawa M., Fukuda K., Ohtani M., Akaza H., Sugimura T., and Wakabayashi K., 1998, Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP, Jpn J Clin Oncol. 28:360–363.PubMedCrossRefGoogle Scholar
  168. Oude Weernink P.A., Verheul E., Kerkhof E., van Veelen C.W., and Rijksen G., 1996, Inhibitors of protein tyrosine phosphorylation reduce the proliferation of two human glioma cell lines, Neurosurgery. 38:108–113.PubMedCrossRefGoogle Scholar
  169. Pagliacci M.C., Smacchia M., Migliorati G., Grignani F., Riccardi C., and Nicoletti I., 1994, Growth-inhibitory effects of the natural phyto-oestrogen genistein in MCF-7 human breast cancer cells, Eur J Cancer 30A:1675–1682.CrossRefGoogle Scholar
  170. Pagliacci M.C., Spinozzi F., Migliorati G., Fumi G., Smacchia M., Grignani F., Riccardi C., and Nicoletti I., 1993, Genistein inhibits tumor cell growth in vitro but enhances mitochrondrial reduction of tetrazolium salst: a further pitfall in the use of the MTT assay for evaluating cell growth and survival, Eur J Cancer 29A:1573–1577.CrossRefGoogle Scholar
  171. Panno M.L., Salerno M., Pezzi V., Sisci D., Maggiolini M., Mauro L., Morrone E.G. and Ando S., 1996, 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. 122:745–749.PubMedCrossRefGoogle Scholar
  172. Park J.H., Oh E. J., Choi Y.H., Kang C.D., Kang H.S., Kim D.K., Kang K.I., and Yoo M.A., 2001, Synergistic effects of dexamethasone and Genistein on the expressions of Cdk inhibitor p21 WAF 1 /CIP 1 in human hepatocellular and colorectal carcinoma cells, Int J Oncol. 18:997–1002.PubMedGoogle Scholar
  173. Peterson G., and Barnes S., 1991, Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene, Biochem Biophys Res Commun. 179: 661–667.PubMedCrossRefGoogle Scholar
  174. Peterson G., and Barnes S., 1993, Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation, Prostate. 22:335–345.PubMedCrossRefGoogle Scholar
  175. Peterson G., and Barnes S., 1996, Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells, Cell Growth Differ. 7:1345–1351.PubMedGoogle Scholar
  176. Peterson T.G., Coward L., Kirk M., Falany C.N., and Barnes S., 1996, The role of metabolism in mammary epithelial cell growth inhibition by the isoflavones genistein and biochanin A, Carcinogenesis 17:1861–1869.PubMedCrossRefGoogle Scholar
  177. Peterson T.G., Ji G.P., Kirk M., Coward L., Falany C.N., and Barnes S., 1998, Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines, Am J Clin Nutr. 68:1505S-1511S.Google Scholar
  178. Plewa M.J., Berhow M.A., Vaughn S.F., Woods E.J., Rundell M., Naschansky K., Bartolini S., and Wagner E.D., 2001, Isolating antigenotoxic components and cancer cell growth suppressors from agricultural by-products, Mutat Res. 480:109–120.PubMedCrossRefGoogle Scholar
  179. Po L.S., Chen Z.Y., Tsang D.S., and Leung L.D., 2002, Baicalein and genistein display differential actions on estrogen receptor (ER) transactivation and apoptosis in MCF-7 cells, Cancer Lett. 187:33–40.PubMedCrossRefGoogle Scholar
  180. Polkowski K., Skierski J.S., and Mazurek A.P., 2000, Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells, Acta Pol Pharm. 57:223–232.PubMedGoogle Scholar
  181. Ponnathpur V., Ibrado A.M., Reed J.C., Ray S., Huang Y., Self S., Bullock G., Nawabi A., and Bhalla K., 1995, Effects of modulators of protein kinases on taxol-induced apoptosis of human leukemic cells possessing disparate levels of p26BCL-2 protein, Clin Cancer Res. 1:1399–1406.PubMedGoogle Scholar
  182. Portoukalian J., Zwingelstein G., Abdul-Malak N., and Dore J.F., 1978, Alteration of gangliosides in plasma and red cells of humans bearing melanoma tumors, Biochem Biophys Res Commun. 85:916–920PubMedCrossRefGoogle Scholar
  183. Pumford S.L., Morton M., Turkes A, and Griffiths K., 2002, Determination of the isoflavonoids Genistein and daidzein in biological samples by gas chromatography-mass spectrometry, Ann Clin Biochem. 39:281–292.PubMedCrossRefGoogle Scholar
  184. Ralph S.J., Wines B.D., Payne M.J., Grubb D., Hatzinisiriou I., Linnane A.W., and Devenish R.J., 1995, Resistance of melanoma cell lines to interferons correlates with reduction of IFN-induced tyrosine phorylation. Induction of the anti-viral state by IFN is prevented by tyrosine kinase inhibitors, J Immunol. 154:2248–2256.PubMedGoogle Scholar
  185. Rao A., Woodruff R., Wade W.N., Kute T.E., and Cramer SD., 2002, Genistein and Vitamin D synergistically inhibit prostatic epithelial cell growth, J Nutr. 132:3191–3194.PubMedGoogle Scholar
  186. Rauth S., Kichina J., and Green A., 1997, Inhibition of growth and induction of differentiation of metastatic melanoma cell sin vitro by Genistein: chemosensitivity is regulated by cellular p53, Br J Cancer. 75:1559–1566.PubMedCrossRefGoogle Scholar
  187. Ravindranath M.H., Morton D.L., 1991. Role of gangliosides in active immunotherapy with melanoma vaccine. Int Rev Immunol. 7:303–329.PubMedCrossRefGoogle Scholar
  188. Ravindranath M.H., Morton D.L., Irie R.F., 1989. An epitope common to gangliosides O-acetyl-GD3 and GD3 recognized by antibodies in melanoma patients after active specific immunotherapy. Cancer Res. 49:3891–3897.PubMedGoogle Scholar
  189. Ravindranath M.H., Tsuchida T., Morton D.L., Irie R.F., 1991. Ganglioside GM3: GD3 ratio as an index for the management of melanoma. Cancer. 67:3029–3035.PubMedCrossRefGoogle Scholar
  190. Rokhlin O.W., and Cohen M.B., 1995, Differential sensitivity of human prostatic cancer cell lines to the effects of protein kinase and phosphatase inhibitors., Cancer Lett. 98:103–110.PubMedGoogle Scholar
  191. Sakamoto K., 2000, Synergistic effects of thearubitin and genistein on human prostate tumor cell (PC-3) growth via cell cycle arrest, Cancer Lett. 151:103–109.PubMedCrossRefGoogle Scholar
  192. Salti G.I., Grewai S., Mehta R.R., Das Gupta T.K., Boddie A.W., J.R. 2000, Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells, Eur J Cancer. 36:796–802.PubMedCrossRefGoogle Scholar
  193. Santell R.C., Kieu N., and Helferich W.G., 2000, Genistein inhibits growth of estrogen-independent human breast cancer cells in culture but not in athymic mice, J Nutr. 130:1665–1669.PubMedGoogle Scholar
  194. Santibanez J.F., Navarro A., and Martinez J., 1997, Genistein inhibits proliferation and in vitro invasive potential of human prostatic cancer cell lines, Aniticancer Res. 17:1199–1204.Google Scholar
  195. Sasamura H., Takahasi A., Miyao N., Yanase M., Masumori N., Kitamura H., Itoh N., and Tsukamoto T, 2002, Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma, Br J Cancer. 86:768–773.PubMedCrossRefGoogle Scholar
  196. Sathyamoorthy N., Gilsdorf J.S., and Wang T.T., 1998, Differential effect of genistein on transforming growth factor beta 1 expression in normal and malignant mammary epithelial cells, Anticancer Res, 18:2449–2453.PubMedGoogle Scholar
  197. Savickieni J., Gineitis A., Shanbhag V.P., and Stigbrand T., 1995, Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation, Anticancer Res. 15:687–692.Google Scholar
  198. Scholar E.M., and Toews M.L., 1994. Inhibition of invasion of murine mammary carcinoma cells by the tyrosine kinase inhibitor genistein, Cancer Lett. 87:159–162.PubMedCrossRefGoogle Scholar
  199. Setchell K.D., Zimmer-Nechemias L., Cai J., and Heubi J.E., 1998, Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life, Am J Clin Nutr. 68:1453S-1461S.Google Scholar
  200. Shao Z.M., Alpaugh M.L., Fontana J.A., and Barsky S.H., 1998a, Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by P21 WAF 1/CIP 1 induction, G2/M arrest, and apoptosis, J Cell Biochem. 69:44–54.PubMedCrossRefGoogle Scholar
  201. Shao Z.M., Shen Z.Z., Fontana J.A., and Barsky S.H., 2000, Genistein’s “ER-dependent and independent” actions are mediated through ER pathways in ER-positive breast carcinoma cell lines, Anticancer Res. 20: 2409–2416.PubMedGoogle Scholar
  202. Shao Z.M., Wu J., Shen Z.Z., and Barsky S.H., 1998c, Genistein inhibits both constitutive and EGF-stimulated invasion in ER-negative human breast carcinoma cell lines, Anticancer Res. 18:1435–1439.PubMedGoogle Scholar
  203. Shao Z.M., Wu J., Shen Z.Z., and Barsky S.H., 1998b, Genistein exerts multiple suppressive effects on human breast carcinoma cells, Cancer Res. 58:4851–4857.PubMedGoogle Scholar
  204. Shelnutt S.R., Cimino C.O., Wiggins P.A., and Badger T.M., 2000, Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein, Cancer Epidemiol Biomarkers Prey. 9:413–419.Google Scholar
  205. Shen F., and Weber G., 1997, Synergistic action of quercetin and Genistein in human ovarian carcinoma cells, Oncol. Res. 9:597–602.PubMedGoogle Scholar
  206. Shen F., Xue X., and Weber G., 1999, Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells, Anticancer Res. 19:1657–1662.PubMedGoogle Scholar
  207. Shen J.C., Klein R., Wei Q., Guan Y., Contois J.H., Wang T.T., Chang S., and Hursting S.D., 2000, Low-dose Genistein induces cyclin-dependent kinase inhibitors and G (1) cell-cycle arrest in human prostate cancer cells, Mol Carcinog. 29:92–102.PubMedCrossRefGoogle Scholar
  208. Simeone D.M., Yule D.I., Logsdon C.D. and Williams J.A., 1995, Ca2+ signaling through secretagogue and growth factor receptors on pancreatic AR42J cells, Regul Pept. 55:197–206.PubMedCrossRefGoogle Scholar
  209. Sjoberg E.R., Chammas R., Ozawa II., Kawashima I., Kho K.H., Morris HR, Dell, A., Tai T and Varki A.,1995, Expression of De-N-actetyl-gangliosides in Human melanoma Cells Is Induced by Genistein or Nocodazole, J Bio Chem. 270:2921–2930.CrossRefGoogle Scholar
  210. So F.V., Guthrie N., Chambers A.F., and Carroll K.K., 1997, Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen, Cancer Lett. 112:127–133.PubMedCrossRefGoogle Scholar
  211. Spinozzi F., Pagliacci M.C., Migliorati G., Moraca R., Grignani F., Riccardi C., and Nicoletti I., 1994, The natural tyrosine kianse inhibitor genistein produces cellcycle arrest and apoptosis in Jurkat T- leukemia cells, Leuk Res. 18:431–439.PubMedCrossRefGoogle Scholar
  212. Steck T.R., and Drlica K., 1984, Bacterial chromosome segregation: evidence for DNA gyrase involvement in decatenation, Cell. 36:1081–1088.PubMedCrossRefGoogle Scholar
  213. Sternglanz R., DiNardo S., Voelkel K.A., Nishimura Y., Hirota Y., Becherer K., Zumstein L., and Wang J.C., 1981. Mutations in the gene coding for Escherichia coli DNA topoisomerase I affect transcription and transposition, Proc Natl Acad Sci USA. 78:2747–2751.PubMedCrossRefGoogle Scholar
  214. Strom S.S, Yamamura Y., Duphorne C.M., Spitz M.R., Babaian R.J., Pillow P.C., and Hursting S.D., 1999, Phytoestrogen intake and prostate cancer: a case-control study using a new database, Nutr Cancer. 33:20–25.PubMedCrossRefGoogle Scholar
  215. Sun X.Y., Plouzek C., Henry J.P., Wang T.T., and Phang J.M., 1998, Increase d UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells, Cancer Res. 58:2379–2384.PubMedGoogle Scholar
  216. Suzuki K., Koike H., Matsui H., Ono Y., Hasumi M., Nakazato H., Okugi H., Sekine Y., Oki K., Ito K., Yamamoto T., Fukabori Y., Kurokawa K., and Yamanaka H., 2002, Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3, Int J Cancer. 99:846–852.PubMedCrossRefGoogle Scholar
  217. Takeda Y., Nishio K., Niitani H., and Saijo N., 1994, Reversal of multidrug resistance by tyrosine-kinase inhibitors in a non-P-glycoprotein-mediated multidrug-resistant cell line, Int J Cancer. 57:229–239.PubMedCrossRefGoogle Scholar
  218. Tanos V., Brzezinski A., Drize O., Strauss N., Peretz T., 2002. Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and malignant epithelial breast cells in vitro. Eur J Obstet Gynecol Reprod Biol. 102:188–194.PubMedCrossRefGoogle Scholar
  219. Thompson D., Whicher J.T., and Evans S.W., 1993, Interleukin 6 signal transduction in a human hepatoma cell line (Hep G2), Immunopharmacol Immunotoxicol. 15:371–386.PubMedCrossRefGoogle Scholar
  220. Tiisala S., Majuri M.L., Carpen O., Renkonen R., 1994, Genistein enhances the ICAM-mediated adhesion by inducing the expression of ICAM-1 and its counter-receptors, Biochem Biophys Res Commun. 203:443–449.PubMedCrossRefGoogle Scholar
  221. Torti M., Marti K.B., Altschuler D., Yamamoto K., and Lapetina E.G., 1992, Erythropoietin induces p21ras activation and p 120GAP tyrosine phosphorylation in human erythroleukemia cells, J Biol Chem. 267:8293–8298.PubMedGoogle Scholar
  222. Traganos F., Ardelt B., Halko N., Bruno S., and Darzynkiewicz Z., 1992, Effects of genistein on the growth and cell cycle progression of normal human lymphocytes and human leukemic MOLT-4 and HL-60 cells. Cancer Res. 52:6200–6208.PubMedGoogle Scholar
  223. Tsujishita Y., Asaoka Y., and Nishizuka Y., 1994, Regulation of phospholipase A2 in human leukemia cell lines: its implication for intracellular signaling, Proc Natl Acad Sci USA. 91:6274–6278.PubMedCrossRefGoogle Scholar
  224. Uckun F.M., Evans W.E., Forsyth C.J., Waddick K.G., Ahlgren L.T., Chelstrom L.M., Burkhardt A., Bolen J., Myers D.E., 1995, Biotherapy of B-cell precursor leukemia by targeting genistein to CD 19-associated tyrosine kinases, Science. 267:886–891.PubMedCrossRefGoogle Scholar
  225. Uckun F.M., Messinger Y., Chen C.L., O’Neill K., Myers D.E., Goldman F., Hurvitz C., Casper J.T., Levine A., 1999, Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD 19-directed tyrosine kinase inhibitor. Clin Cancer Res. 5:3906–3913.PubMedGoogle Scholar
  226. Uckun F.M., Narla R.K., Jun X., Zeren T., Venkatatchalam T., Waddick K.G., Rostostev A., and Myers D.E., 1998, Cytototoxic activity of epidermal growth factor-genistein against breast cancer cells, Clin Cancer Res. 4:901–912.PubMedGoogle Scholar
  227. Upadhyay S., Neburi M., Chinni S.R., Alhasan S., Miller F., and Sarkar F.H., 2001, Differential sensitivity of normal and malignant breast epithelial cells to genistein is partly mediated by p21 (WAF1), Clin Cancer Res. 7:1782–1789.PubMedGoogle Scholar
  228. van Rijn J., van den Berg J.,1997, Flavonoids as enhancers of x-ray-induced cell damage in hepatoma cells., Clin Cancer Res. 3:1775–1779.PubMedGoogle Scholar
  229. Veldman C.M., Schmid C., 1998, Differential effects of fluroide and insulin-like growth factor I on sodiumdependent alanine and phosphate transport in a human osteoblast-like cell line, Growth Horm IGF Res. 8:55–63.PubMedCrossRefGoogle Scholar
  230. Venkatakrishnan G.S.R., and Groopman J.E., 2000, Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells, J Biol Chem. 275:6868–6875.PubMedCrossRefGoogle Scholar
  231. Verma S.P., Salamone E., and Goldin B., 1997, Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides, Biochem Biophys Res Commun. 233:692–696.PubMedCrossRefGoogle Scholar
  232. Versantvoort C.H., Rodes T., and Twentyman P.R., 1996, Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds, Br J Cancer. 74:1949–1954.PubMedCrossRefGoogle Scholar
  233. Wang C., and Kurzer M.S., 1998, Effects of phytoestrogens on DNA synthesis in MCF-7 cells in the presence of estradiol or growth factors, Nutr Cancer. 31:90–100.PubMedCrossRefGoogle Scholar
  234. Wang T.T., Sathyamoorthy N., Phang J.M., 1996. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis. 17:272–275.Google Scholar
  235. Watanabe S., Yamaguchi M., Sobue T., Takahashi T., Miura T., Arai Y., Mazur W., Wahala K., and Adlercreutz H., 1998. Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako), J Nutr. 128:1710–1715.PubMedGoogle Scholar
  236. Weber G., Shen D.F., Li W., Yang H., Look K.Y., Abonyi M., and Prajda N., 2000, Signal transduction and biochemical targeting of ovarian carcinoma, Eur J Gynaecol Oncol. 21:231–236.PubMedGoogle Scholar
  237. Wegenka U.M., Lutticken C., Buschmann J., Yuan J., Lottspeich F., Muller-Esterl W., Schindler C., Roeb E., Heinrich P.C., and Horn F., 1994, The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family, Mol Cell Biol. 14:3186–3196.PubMedGoogle Scholar
  238. Willard S.T., and Frawley L.S., 1998, Phytoestrogens have agonistic and combinatorial effects on estrogenresponsive gene expression in MCF-7 human breast cancer cells, Endocrine. 8:117–121.PubMedCrossRefGoogle Scholar
  239. Xiang H., Schevzov G., Gunning P., Williams HM., and Silink M., 2002, A comparative study of growth-inhibitory effects of isoflavones and their metabolites on human breast and prostate cancer cell lines, Nutr Cancer. 42:224–232.PubMedCrossRefGoogle Scholar
  240. Xu J., and Loo G., 2001, Different effects of genistein on molecular markers related to apoptosis in two phenotypically dissimilar breast cancer cell lines, J Cell Biochem. 82:78–88.PubMedCrossRefGoogle Scholar
  241. Yabunaka N., 1995, Studies on the regulation of glycolipid sulfotransferase activity in human renal cancer cells, Hokkaido Igaku Zasshi. 70:289–300.PubMedGoogle Scholar
  242. Yabunaka N., Honke K., Ishii A., Ogiso Y., Kuzumaki N., Agishi Y., and Makita A., 1997, Involvement of Ras in the expression of glycolipid sulfotransferase in human renal cancer cells, Int J Cancer. 71:620–630.PubMedCrossRefGoogle Scholar
  243. Yamada A., Hara A., Inoue M., Kamizono S., Higuchi T., and Itoh K., 1997, Beta 2-integrin-mediated signal up-regulates counterecptor ICAM-1 expression on human monocytic cell line THP-1 through tyrosine phosphorylation, Cell Immunol. 178:9–16.PubMedCrossRefGoogle Scholar
  244. Yamamoto S., Sobue T., Sasaki S., Kobayashi M., Arai Y., Uehara M., Adlercreutz H., Watanabe S., Takahashi T., Litoi Y., Iwase Y., Akabane M., and Tsugane S., 2001, Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine isoflavones, J Nutr. 131:2741–2747.PubMedGoogle Scholar
  245. Yamane M., and Abe A., 2000, Omega-hydroxylation activity toward leukotriene B (4) and polyunsaturated fatty acids in the human hepatoblastoma cell line, HepG2, and human lung adenocarcinoma cell line, A549, J Biochem. 128:827–835.PubMedCrossRefGoogle Scholar
  246. Yamashita K., Suzuki M., Iwata H., Koike T., Hamaguchi M., Shinagawa A., Noguchi T., and Hayakawa T., 1996. Tyrosine phosphorylation is crucial for growth signaling by tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), FEBS Lett. 396:103–107.PubMedCrossRefGoogle Scholar
  247. Yan C., and Han R., 1999, Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT 1080 human fibrosarcoma cells, Zhonghua Zhong Liu Za Zhi. 21:171–174.PubMedGoogle Scholar
  248. Yanagihara K., Ito A., Toge T., and Numoto M., 1993, Antiproliferative effects of isoflavones on human cancer cell lines established from the gstrointestinal tract, Cancer Res. 53:5815–5821.PubMedGoogle Scholar
  249. Yang C.C., Hsu C., Sheu J.C, Mai X.Y., and Yang S.D., 1998, Differential tyrosine phosphorylation/activation of oncogenic proline-directed protein kinase F (A)/GSK-3alpha in well and poorly differentiated human prostate carcinoma cells, J Protein Chem. 17:329–335.PubMedCrossRefGoogle Scholar
  250. Yang E.B., Wang D.F., Mack P., and Cheng L.Y., 1996, Genistein, a tyrosine kinase inhibitorm reduces EGF-induced EGF receptor internalization and degradation in human hepatoma HepG2 cells, Biochem Biophs Res Commun. 224:309–317.CrossRefGoogle Scholar
  251. Yu J., Cheng Y., Xie L., and Zhang R., 1999, Effects of genistein and daidzein on membrane characteristics of HCT cells, Nutr Cancer. 33:100–104.PubMedCrossRefGoogle Scholar
  252. Yu L., Blackburn G.L., and Zhou JR., 2003, Genistein and daidzein downregulate prostate androgen-regulated transcript- 1 (PART 1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells, J Genistein Prostate Cancer. 133:389–392.Google Scholar
  253. Yun J., Lee C.K., Chang I.M., Takatsu K., Hirano T., Min K.R., Lee M.K., and Kim Y., 2000, Differential inhibitory effects of sophoricoside analogs on bioactivity of several cytokines, Life Sci. 67:2855–2863.PubMedCrossRefGoogle Scholar
  254. Zheng W., Dai Q., Custer L.J., Shu X.O., Wen W.Q., Jin F., Franke A.A., 1999, Urinary excretion of isoflavonoids and the risk of breast cancer, Cancer Epidemiol Biomarkers Prey. 8:35–40.Google Scholar
  255. Zhu Q., Meisinger J., Van Thiel D.H., Zhang Y., and Mobarhan S., 2002, Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells, Nutr Cancer. 42:131–140.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Mepur H. Ravindranath
    • 1
  • Sakunthala Muthugounder
  • Naftali Presser
  • Subramanian Viswanathan
  1. 1.Laboratory of GlycoimmunotherapyJohn Wayne Cancer InstituteSanta MonicaUSA

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