Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Natural Modulators of Estrogen Biosynthesis and Function as Chemopreventive Agents

  • Bhat, Krishna P.L. (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois) ;
  • Pezzuto, John M. (Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois)
  • Published : 2001.12.01
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Abstract

There is clearly a need for novel breast cancer chemopreventive agents with enhanced potency and specificity with tittle or no side effects. To this end, several new chemical moieties have been synthesized or isolated from natural sources. In this reviewal we have described some agents currently in use or under development for treatment or prevention of breast cancer, as well as our own strategies for the discovery of natural product modulators of estrogen biosynthesis and function. In particulars bioassay-guided fractionation of active plant extracts is a unique method for identifying agents with novel mechanisms of action, some of which should be useful for prevention of human cancer. Further, with the advent of combinatorial chemistry and high throughput screening, even greater progress may now be expected with natural product leads.

Keywords

References

  1. Environ. Health Perspect. v.103 Phytoestrogens: epidemiology and a possible role in cancer protection Adlercreutz,H.
  2. J. Natl. Cancer Inst. v.86 Estrogen metabolism and excretion in Oriental and Caucasian women Adlercreutz,H.;Gorbach,S.L.;Goldin,B.R.;Woods,M.N.;Dwyer,J.T.;Hamalainen,E.
  3. Lancet v.339 Dietary phyto-oestrogens and the menopause in Japan Adlercreutz,H.;Hamalainen,E.;Gorbach,S.;Goldin,B.
  4. J. Biol. Chem. v.262 Genistein, a specific inhibitor of tyrosine-specific protein kinases Akiyama,T.;Ishida,J.;Nakagawa,S.;Ogawara,H.;Watanabe,S.;Itoh,N.;Shibuya,M.;Fukami,Y.
  5. Cancer Res. v.50 Estrogen regulation of placental alkaline phosphaste gene expression in a human endometrial adenocarcinoma cell line Albert,J.L.;Sundstrom,S.A.;Lyttle,C.R.
  6. Cancer Res. v.49 Stimulatory effects of 4-hydroxytamoxifen on proliferation of human endometrial adenocarcinoma cells(Ishikawa line) Anzai,Y.;Holinka,C.F.;Kuramoto,H.;Gurpide,E.
  7. Breast Cancer Res. Treat. v.46 The chemopreventive properties of soy isoflavonoids in animal models of breast cancer Barnes,S.
  8. Aus. Vet. J. v.22 A specific breeding problem of sheep on subterranean clover pastures in western Australia Bennetts,H.W.;Underwood,E.J.;Shier,F.L.
  9. Cancer Res. v.61 Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models Bhat,K.P.L.;Lantvit,D.;Christov,K.;Mehta,R.G.;Moon,R.C.;Pezzuto,J.M.
  10. Cancer Res. v.61 Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (lshikawa) cells Bhat,K.P.L.;Pezzuto,J.M.
  11. Chem. Res. Toxicol. v.13 Role of quinones in toxicology Bolton,J.L.;Trush,M.A.;Penning,T.M.;Dryhurst,G.;Monks,T.J.
  12. J. Enzyme Inhib. v.4 Biochemical and molecular aspects of aromatase Brueggemeier,R.W.
  13. Eur. J. Obstet. Gynecol. Reprod. Biol. v.85 Phytoestrogens: the "natural" selective estrogen receptor modulators? Brzezinski,A;Debi,A.
  14. Mol. Cell. Endocrinol. v.6 Cytochrome P-450 and the aromatization of 16alpha-hydroxytestosterone and androstenedione by human placental microsomes Canick,J.A.;Ryan,K.J.
  15. Prim. Care Update Ob. Gyns. v.7 Phytoestrogens as hormone replacement therapy: an evidence-based approach Carusi,D.
  16. Chem. Res. Toxicol. v.13 A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines Chen,Y.;Liu,X.;Pisha,E.;Constantinou,A.I.;Hua,Y.;Shen,L.;van Breemen,R.B.;Elguindi,E.C.;Blond,S.Y.;Zhang,F.;Bolton,J.L.
  17. Br. Med. J. v.295 Cervical adenocarcinoma and oral contraceptives Chilvers,C.;Mant,D.;Pike,M.C.
  18. Bioorg. Med. Chem. Lett. v.9 Synthesis and sulfatase inhibitory activities of (E)- and (Z)-4-hydroxytamoxifen a sulfamates Chu,G.H.;Peters,A.;Selcer,K.W.;Li,P.K.
  19. Breast Cancer Res. v.2 Estrogen receptor transaction: Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action Curtis Hewitt,S.;Couse,J.F.;Korach,K.S.
  20. Br. Med. Bull. v.56 Novel agents to modulate oestrogen action Dardes,R.C.;Jordan,V.C.
  21. Am. J. Physiol. v.263 PDGF induces tyrosine phosphorylation in osteoblast-like cells: relevance to mitogenesis Davidai,G.;Lee,A.;Schvartz,I.;Hazum,E.
  22. Cancer. Res. v.52 Antitumoral and endocrine effects of (+)-vorozole in rats bearing dimethylbenzanthracene-induced mammary tumors De Coster,R.;Van Ginckel,R.F.;Callens,M.J.;Goeminne,N.K.;Janssens,B.L.
  23. Environ. Health Perspect. v.105 Dietary estrogens stimulate human breast cells to enter the cell cycle Dees,C.;Foster,J.S.;Ahamed,S.;Wimalasena,J.
  24. J. Steroid Biochem. Mol. Biol. v.37 4-Aminoandrostenedione derivatives: a novel class of irrebersible aromatase inhibitors. Comparison with FCE 24304 and 4-hydroxyandrostenedione Di Salle,E.;Giudici,D.;Ornati,G.;Briatico,G.;DAlessio,R.;Villa,V.;Lombardi,P.
  25. Cancer Res. v.53 Inhibition of estrone sulfatase activity by estrone-3-methylthiophosphonate: a potential therapeutic agent in breast cancer Duncan,L.;Purohit,A.;Howarth,N.M.;Potter,B.V.;Reed,M.J.
  26. Anticancer Res. v.16 MCF-7 cell cycle arrested at G1 through ursolic acid, and increased reduction of tetrazolium salts Es-Saady,D.;Simon,A.;Jayat-Vignoles,C.;Chulia,A.J.;Delage,C.
  27. J. Endocrinol. v.147 Inhibition of 5-alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids Evans,B.A.;Griffiths,K.;Morton,M.S.
  28. Cancer Epidemiol. Biomarkers Prev. v.7 Soy, its components, and cancer prevention: a review of the in vitro, animal, and human data Fournier,D.B.;Erdman,J.W.Jr.;Gordon,G.B.
  29. Gen. Pharmacol. v.28 Antiestrogenic compounds infibit estrogen-induced expressions of basic fibroblast growth factor and its mRNA in well-differentiated endometrial cancer cells Fujimoto,J.;Hori,M.;Ichigo,S.;Hirose,R.;Tamaya,T.
  30. Gynecol. Endocrinol. v.10 Estrogen induces expression of c-fos and c-jun via activation of protein kinase C in an endometrial cancer cell line and fibroblasts derived from human uterine endometrium Fujimoto,J.;Hori,M.;Ichigo,S.;Morishita,S.;Tamaya,T.
  31. Cancer Lett. v.141 Progestins suppress estrogen-induced expression of vascular endotherlial growth factor (VEGF) subtypes in uterine endometrial cancer cells Fujimoto,J.;Sakaguchi,H.;Hirose,R.;Ichigo,S.;Tamaya,T.
  32. Postgrad. Med. v.35 Selective estrogen receptor modulators. An aid in unraveling the links between estrogen and breast cancer Fuqua,S.A.;Russo,J.;Shackney,S.E.;Stearns,M.E.
  33. Gynecol. Oncol. v.13 A new human cell line derived from a poorly differentiated endometrial adenocarcinoma Gal,D.;Froney,J.P.;Dev,V.G.;Porter,J.C.
  34. J. Clin. Oncol. v.12 Current perspectives on aromatase inhibitors in breast cancer Goss,P.E.;Gwyn,K.M.
  35. J. Clin. Endocrinol. Metab. v.63 Effects of estradiol on deoxyribonucleic acid polymerase alpha activity in the Ishikawa human endometrial adenocarcinoma cell line Gravanis,A.;Gurpide,E.
  36. N. Engl. J. Med. v.285 Vaginal cancer after maternal treatment with synthetic estrogens Greenwald,P.;Barlow,J.J.;Nasca,P.C.;Burnett,W.S.
  37. Proc. Natl. Acad. USA v.96 Hormnal prevention of breast cancer: mimicking the protective effect of pregnancy Guzman,R.C.;Yang,J.;Rajkumar,L.;Thordarson,G.;Chen,X.;Nandi,S.
  38. J. Steroid Biochem. Mol. Biol. v.42 Immunocytochemical determination of estrogen and progesterone receptors in human endometrial adenocarcinoma cell (lsikawa cells) Hata,H.;Kuramoto,H.
  39. Steroids v.50 Estrogens and benign prostatic hyperplasia: the basis for aromatase inhibitor therapy Henderson,D.;Habenicht,U.F.;Nishino,Y.;el Etreby,M.F.
  40. Cancer Res. v.48 Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture Henderson,B.E.;Ross,R.;Bernstein,L.
  41. Cancer v.8 Clear cell adenocarcinoma and the current status of DES-exposed females Herbst,A.L.
  42. Can. J. Biochem. Cell. Biol. v.63 Steroid sulfotransferases and steroid sulfate sulfatases: characteristics and biological roles Hobkirk,R.
  43. J. Steroid Biochem. v.24 Responses to estradiol in a human endometrial adenocarcinoma cell line (Ishikawa) Holinka,C.F.;Hata,H.;Kuramoto,H.;Gurpide,E.
  44. J. Med. Chem. v.37 Estrone sulfamates: potent inhibitors of estrone sulfatase with therapeutic potential Howarth,N.M.;Purohit,A.;Reed,M.J.;Potter,B.V.
  45. Cancer Res. v.58 Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo Hsieh,C.Y.;Santell,R.C.;Haslam,S.Z.;Helferich,W.G.
  46. Cancer Res. v.54 Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Huang,M.T.;Ho,C.T.;Wang,Z.Y.;Ferraro,T.;Lou,Y.R.;Stauber,K.;Ma,W.;Georgiadis,C.;Laskin,J.D.;Conney,A.H.
  47. Science v.275 Cancer chemopreventive activity of resveratrol, a natural product derived from grapes Jang,M.;Cai,L.;Udeani,G.O.;Slowing,K.V.;Thomas,C.F.;Beecher,C.W.;Fong,H.H.;Farnsworth,N.R.;Kinghorn,A.D.;Mehta,R.G.;Moon,R.C.;,Pezzuto,J.M.
  48. coreanus. Arch. Pharmacal Res. v.23 Aromatase inhibitors from Isodon excisus var. Jeong,H.J.;Chang,L.C.;Kim,J.K.;Kim,I.K.;Kinghorn,A.D.;Pezzuto,J.M.
  49. Eur. J. Cancer v.12 Effect of tamoxifen (ICI 46,474) on initiation and growth of DMBA-induced rat mammary carcinomata Jordan,V.C.
  50. Biol. Reprod. v.54 Estrogen receptors: bioactivities and interactions with cell signaling pathways Katzenellenbogen,B.S.
  51. J. Steroid Biochem. Mol. Biol. v.74 Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology Katzenellenbogen,B.S.;Choi,I.;Delage-Mourroux,R.;Ediger,T.R.;Martini,P.G.;Montano,M.;Sun,J.;Weis,K.;Katzenellenbogen,J.A.
  52. Breast Cancer Res. Treat. v.44 Mc Guire Memorial Lecture. Antiestrogens: mechanisms of action and resistance in breast cancer Katzenellenbogen,B.S.;Montano,M.M.;Ekena,K.;Herman,M.E.;Mclnerney,E.M.;William,L.
  53. Acta Obstet. Gynecol. Scand. v.72 Changing concepts of medical treatment of endometriosis Kauppila,A.
  54. Arch. Oral. Biol. v.40 Protein tyrosine phosphorylation induced by epidermal growth factor and insulin-like growth factor-l in a rat clonal dental pulp-cell line Kawase,T.;Orikasa,M.;Ogata,S.;Burns,D.M.
  55. J. Biol. Chem. v.262 Purification and characterization of human placental aromatase cytochrome P-450 Kellis,J.Jr.;Vickery,L.E.
  56. Cancer Epidemiol. Biomarkers Prev. v.7 Aromatase inhibitors as potential cancer chemopreventives Kelloff,G.J.;Lubet,R.A.;Lieberman,R.;Eisenhauer,K.;Steele,V.E.;Crowell,J.A.;Hawk,E.T.;Boone,C.W.;Sigman,C.C.
  57. J. Steroid. Biochem. Mol. Biol. v.44 Growth suppression of MCF-7 human breast cancer cells by aromatase inhibitors: a new system for aromatase inhibitor screening Kitawaki,J.;Kim,T.;Kanno,H.;Noguchi,T.;Yamamoto,T.;Okada,H.
  58. J. Nat. Prod. v.60 Biocative constituents of Morus australis and Broussonetia papyrifera Ko,H.H.;Yu,S.M.;Ko,F.N.;Teng,C.M.;Lin,C.N.
  59. Proc. Natl. Acad. Sci. USA v.93 Cloning of a novel receptor expressed in rat prostate and ovary Kuiper,G.G.;Enmark,E.;Pelto-Huikko,M.;Nilsson,S.;Gustafsson,J.A.
  60. Am. J. Clin. Nutr. v.68 Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity Lamartiniere,C.A.;Zhang,J.X.;Cotroneo,M.S.
  61. C. A Cancer J. Clin. v.49 Cancer statistics Landis,S.H.;Murray,T.;Bolden,S.;Wingo,P.A.
  62. Cancer Lett. v.130 Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids Le Bail,J.C.;Varnat,F.;Nicolas,J.C.;Habrioux,G.
  63. J. Nat. Prod. Aromatase inhibitors from Broussonetia papyrifera Lee,D.;Bhat,K.P.L.;Fong,H.H.S.;Farnsworth,N.R.;Pezzuto,J.M.;Kinghorn,A.D.
  64. Cancer Res. v.50 Development of antiestrogens and their use in breast cancer: eighth Cain memorial award lecture Lerner,L.J.;Jordan,V.C.
  65. J. Steroid Biochem. Mol. Biol. v.59 Characterization of the functional progesterone receptor in an endometrial adenocarcinoma cell line (Ishikawa): progesterone-induced expression of the alpha1 integrin Lessey,B.A.;Ilesanmi,A.O.;Castelbaum,A.J.;Yuan,L.;Somkuti,S.G.;Chwalisz,K.;Satyaswaroop,P.G.
  66. J. Biol. Chem. v.261 Cytochrome P-450-mediated redox cycling of estrogens Liehr,J.G.;Ulubelen,A.A.;Strobel,H.W.
  67. Am. J. Obstet. Gynecol. v.149 Plasma steroid hormones, cytosol receptors, and thymidine incorporation rate in endometrial carcinoma Lindahl,B.;Alm,P.;Ferno,M.;Norgren,A.;Trope,C.
  68. J. Am. Coll. Cardiol. v.35 Phytoestrogens and cardiovascular health Lissin,L.W.;Cooke,J.P.
  69. Endocrinology v.127 A simple and sensitive microtiter plate estrogen bioassay based on stimulation of alkaline phosphatase in Ishikawa cells: estrogenic action of delta 5 adrenal steroids Littlefield,B.A.;Gurpide,E.;Markiewicz,L.;McKinley,B.;Hochberg,R.B.
  70. Carcinogenesis v.15 Chemopreventive effects of the aromatase inhibitors vorozole (R-83842) and 4-hydroxyandrostenedione in the methylnitrosourea (MNE)-induced mammary tumor model in Sprague-Dawley rats Lubet,R.A.;Steele,V.E.;Casebolt,T.L.;Eto,I.;Kelloff,G.J.;Grubbs,C.J.
  71. Pharmacol. Rev. v.50 Basic guide to the mechanisms of antiestrogen action MacGregor,J.I.;Jordan,V.C.
  72. Endocrinology v.123 The hydrolysis of estrone sulfate and dehydropiandrosterone sulfate by MCF-7 human breast cancer cells Maclndoe,J.H.
  73. Environ. Health Perspect. v.102 Dietary estrogens act through estogen receptor-mediated processes and show no antiestrogenicity in cultured breast cancer cells Makela,S.;Davis,V.L.Tally,W.C.;Korkman,J.;Salo,L.;Vinko.R.;Santti,R.;Korach,K.S.
  74. Eur. J. Pharmacol. v.334 Effect of selected triterpenoids on chronic dermal inflammation Manez,S.;Recio,M.C.;Giner,R.M.;Rios,J.L.
  75. Cancer Res. v.43 Effect of tamoxifen and α-difluoromethylornithine on clones of nitrosomethylurea-induced rat mammary tumor cells grown in soft agar culture Manni,A.;Wright,C.
  76. J. Steroid. Biochem. Mol. Biol. v.58 Evidence of in situ estrogen synthesis in nitrosomethylurea-induced rat mammary tumors via the enzyme estrone sulfatase Masamura,S.;Santner,S.J.;Santen,R.J.
  77. Am. J. Clin. Nutr. v.68 Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast McMichael-Phillips,D.F.;Harding,C.;Morton,M.;Roberts,S.A.;Howell,A.;Potten,C.S.;Bundred,N.J.
  78. Nature v.334 The human oestrogen receptor functions in yeast Metzger,D.;White,J.H.;Chambon,P.
  79. Anticancer Res. v.14 Chemoprevention of MNU-induced mammary tumorigenesis by hormone response modifier: toremifene, RU16117, tamoxifen, aminoglutethimide and progesterone Moon,R.C.;Steele,V.E.;Kelloff,G.J.;Thomas,C.F.;Detrisac,C.J.;Mehta,R.G.;Lubet,R.A.
  80. Cell Prolif. v.31 Sulindac enhances cell proliferation in DMH-treated mouse colonic mucosa Moorghen,M.;Orde,M.;Finney,K.J.;Appleton,D.R.;Watson,A.J.
  81. Proc. Natl. Acad. Sci. USA v.92 Hormones and mammary carcinogenesis in mice, rats and humans: a unifying hypothesis Nandi,S.;Guzman,R.C.;Yang,J.
  82. J. Steroid Biochem. Molec. Biol. v.46 Action of danazol on the conversion of estrone sulfate to estradiol and on the slfatase activity in the MCF-7, T-47D and MDA-MB-231 human mammary cancer cells Nguyen,B.L.;Ferme,I.;Chetrittte,G.;Pasqualini,J.R.
  83. Nippon Sanka Fujinka Gakkai Zasshi v.37 Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors Nishida,M.;Kasahara,K.;kaneko,M.;Iwasaki,H.;Hayashi,K.
  84. Obset. Gynecol. v.46 Liver tumors and oral contraceptives Nissen,E.D.;Kent,D.R.
  85. Arch. Pharm. Res. v.21 Induction of differentiation of the cultured rat mammary epithelial cells by triterpene acids Paik,K.J.;Jeon,S.S.;Chung,H.Y.;Lee,K.H.;Kim,K.W.;Chung,J.K.;Kim,N.D.
  86. J. Endocrinol. v.150 Control and expression of oestrone sulphatase activities in human breast cancer Pasqualini,J.R.;Chetrite,G.;Nestour,E.L.
  87. Mol. Endocrinol v.6 Ligand-dependent and -independent function of the transactivation regions of the human estrogen receptor in yeast Pham,T.A.;Hwung,Y.P.;Santiso-Mere,D.;McDonnell,D.P.;O'Malley,B.W.
  88. Meth. Cell Science v.19 Cell-based assay for the determination of estrogenic and anti-estrogenic activities Pisha,E.;Pezzuto,J.M.
  89. Chem. Res. Toxicol. v.14 Evidence that a metabolite of equine estrogens, 4-hydroxyeuilenin, induces cellular transformation in vitro Pisha,E.;Lui,X.;Constantinou,A.I.;Bolton,J.L.
  90. Biochemistry v.34 Inactivation of steroid sulfatase by an active stie-directed inhibitor, estrone-3-O-sulfamate Purohit,A.;Williams,G.J.;Howarth,N.M.;Potter,B.V.;Reed,M.J.
  91. Mol. Cell. Endocrinol. v.171 Nonsteroidal and steroidal sulfamates: new drugs for cancer therapy Purohit,A.;Woo,L.W.;Barrow,D.;Hejaz,H.A.;Nicholson,R.I.;Potter,B.V.;Reed,M.J.
  92. J. Clin. Pharm. Ther. v.23 A review of the newer aromatase inhibitors in the management of metastatic breast cancer Reddy,P.
  93. Cancer Res. v.50 Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone and in vitro tumor aromatase activity in postmenopausal women with breast cancer Reed,M.J.;Lai,L.C.;Owen,A.M.;Singh,A.;Coldman,N.G.;Purohit,A,Ghilchik,M.W.,Shaikh,N,A;James,V.H>
  94. Cancer v.58 zInternational comparision of mortality rates for cancer of the breast, ovary, prostate and colon, per capita fat consumtion Rose,D.P.;Boyer,A.P.;Wynder,E.L.
  95. J. Clin. Invest v.51 Estrone sulfate: production rate and metabolism in man Ruder,H.J.;Loriaux,L.;Lipsett,M.B.
  96. Ann. N. Y. Acad. Sci. v.464 Enzymatic control of estrogen production in human breast cancer: relative significance of aromatase versus sulfatase pathway Santen,R.J.;Leszezynski,D.;Tilson-Mallet,N.;Feil,P.D.;Wright,C.;Manni,A.;Santner,S.J.
  97. J. Clin. Endocrinol. v.59 In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway Santner,S.J.;Feil,P.D.;Santen,R.J.
  98. Cancer Res. v.58 Genistein exerts multiple suppressive effects on human breast carcinoma cells Shao,Z.M.;Wu,J.;Shen,Z.Z.;Barsky,S.H.
  99. Br. J. Obstet. Gynaecol. v.94 Adverse long-term effects of oral contraceptives: a review Shaw,R.W.
  100. Cancer Res. v.57 Blockade of the stimulatory effect of estrogens OH-tamoxifen, OH-toremifene, droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells Simard,J.;Sachez,R.;Poirier,D.;Gauthier,S.;Singh,S.M.;Merand,Y.;Belanger,A.;Labrie,C.;Labrie,F.
  101. Cancer Res. v.59 Cancer chemopreventive activity mediated by 4¹-bromoflavone, a potent inducer of phase Ⅱ detoxification enzymes Song,L.L.;Kosmeder,J.W.Ⅱ;Lee,S.K.;Gerhauser,C.;Lantvit,D.;Moon,R.C.;Moriarty,R.M.;Pezzuto,J.M.
  102. Environ. Health Perspect. v.103 The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants Soto,A.M.;Sonnenschein,C.;Chung,K.L.;Fernandez,M.F.;Olea,N.;Serrano,F.O.
  103. Cancer Res. v.60 Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells Subbaramaiah,K.;Michaluart,P.;Sporn,M.B.;Dannenberg,A.J.
  104. Environ. Health Perspect. v.105 Neoplastic transformation of cultured mammalian cells by estrogens and estrogens like chemicals Tsutshui,T.;Barret,J.C.
  105. Bio. Pharm. Bull. v.24 Comparative study on reduction of bone loss and lipid metabolism abnormality in ovariectomized rats by soy isolflavones, daidzin, genistin, and glycitin Uesugi,T.;Toda,T.;Tsuji,K.Ishida,H.
  106. Semin. Oncol. v.23 Hormonal approaches to breast cancer treatment and prevention: an overview Vogel,C.L.
  107. Nutr. Cancer v.28 Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells Wang,C.;Kurzer,M.S.
  108. Carcinogenesis v.17 Molecular effects of genistein on estrogen receptor mediated pathways Wang,T.T.;Sathyamoorthy,N.;Phang,J.M.
  109. Steroids v.57 Effects of a normal, human-concentration, phytoestrogen diet on rat uterine growth Whitten,P.L.;Russell,E.;Naftolin,F.
  110. J. Steroid Biochem. Mol. Biol. v.44 Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells Yamamoto,T.;Kitawaki,J.;Urabe,M.;Honjo,H.;Tamura,T.;Noguchi,T.;Okata,H.;Sasaki,H.;Tada,A.;Terashima,Y.
  111. Biochem. Mol. Biol. Int. v.37 Mutations in DNA polymerase beta mRNA of stilbene estrogen-induced kidney tumors in Syrian hamster Yan,Z.J.;Roy,D.
  112. Cancer Res. v.54 A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene Yue,W.;Zhou,D.;Chen,S.;Brodie,A.
  113. Eur. J. Cancer v.27 Comparison of the effects of the irreversible aromatase inhibitor exemestane and MDL 18962 in rats with DMBA-induced mammary tumours Zaccheo,T.;Giudici,D.;Ornati,G.;Penzeri,A.;di Salle,E.
  114. J. Biol. Chem. v.275 Identification of selective estrogen receptor modulators by their gene expression fingerprints Zajchowski,D.A.;Kauser,K.;Zhu,D.;Webster,L.;Aberle,S.;White,F.A.Ⅲ.;Liu,H.L.;Humm,R.;MacRobbie,J.;Ponte,P.;Hegele-Hartung,C.;Knauthe,R.;Fritzemeier,K.H.;Vergona,R.;Rubanyi,G.M.
  115. Cancer Res. v.50 Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening Zhou,D.J.;Pompon,D.;Chen,S.A.
  116. Cancer Res. v.58 Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis Zhou,J.R.;Mukherjee,P.;Gugger,E.T.;Tanaka,T.;Black-burn,G.L.;Clinton,S.K.
  117. Cancer Res. v.56 In vivo activity of 4-methyl-coumarin-7-O-sulfamate, a nonsteroidal, nonestrogenic steroid sulfatase inhibitor Purohit,A.;Woo,L.W.;Singh,A.;Winterborn,C.J.;Potter,B.V.;Reed,M.J.
  118. Anticancer Res. v.11 Antitumor effect of pyridoglutethimide, an aromatase inhibitor, on 7,12-dimethylbenz(a)anthracene-induced mammary tumors of rat Yamamoto,T.;Urabe,M.;Tamura,T.;Kitawaki,J.;Honjo,H.;Okada,H.