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Title: (Anti)estrogenic effects of phytochemicals on human primary mammary fibroblasts, MCF-7 cells and their co-culture

In the public opinion, phytochemicals (PCs) present in the human diet are often considered beneficial (e.g. by preventing breast cancer). Two possible mechanisms that could modulate tumor growth are via interaction with the estrogen receptor (ER) and inhibition of aromatase (CYP19). Multiple in vitro studies confirmed that these compounds act estrogenic, thus potentially induce tumor growth, as well as aromatase inhibitory, thus potentially reduce tumor growth. It is thought that in the in vivo situation breast epithelial (tumor) cells communicate with surrounding connective tissue by means of cytokines, prostaglandins and estradiol forming a complex feedback mechanism. Recently our laboratory developed an in vitro co-culture model of healthy mammary fibroblasts and MCF-7 cells that (at least partly) simulated this feedback mechanism (M. Heneweer et al., TAAP vol. 202(1): 50-58, 2005). In the present study biochanin A, chrysin, naringenin, apigenin, genistein and quercetin were studied for their estrogenic properties (cell proliferation, pS2 mRNA) and aromatase inhibition in MCF-7 breast tumor cells, healthy mammary fibroblasts and their co-culture. The proliferative potency of these compounds in the MCF-7 cells derived from their EC{sub 50}s decreased in the following order: estadiol (4*10{sup -3} nM) > biochanin A (9 nM) > genistein (32 nM) > testosteronemore » (46 nM) > naringenin (287 nM) > apigenin (440 nM) > chrysin (4 {mu}M). The potency to inhibit aromatase derived from their IC{sub 50}s decreased in the following order: chrysin (1.5 {mu}M) > naringenin (2.2 {mu}M) > genistein (3.6 {mu}M) > apigenin (4.1 {mu}M) > biochanin A (25 {mu}M) > quercetin (30 {mu}M). The results of these studies show that these PCs can induce cell proliferation or inhibit aromatase in the same concentration range (1-10 {mu}M). Results from co-cultures did not elucidate the dominant effect of these compounds. MCF-7 cell proliferation occurs at concentrations that are not uncommon in blood of individuals using food supplements. Results also indicate that estrogenicity of these PCs is quantitatively more sensitive than aromatase inhibition. It is suggested that perhaps a more cautionary approach should be taken for these PCs before taken as food supplements.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2]
  1. Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80177, 3508 TD Utrecht (Netherlands). E-mail: J.A.vanMeeuwen@iras.uu.nl
  2. Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80177, 3508 TD Utrecht (Netherlands)
  3. St. Antonius Hospital, PO 2500, 3430 EM Nieuwegein (Netherlands)
  4. Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven (Netherlands)
Publication Date:
OSTI Identifier:
20976965
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.03.016; PII: S0041-008X(07)00134-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL GROWTH; BLOOD; CELL PROLIFERATION; CONNECTIVE TISSUE; ESTRADIOL; FIBROBLASTS; FOOD; HUMAN POPULATIONS; IN VITRO; IN VIVO; INHIBITION; LYMPHOKINES; MAMMARY GLANDS; NEOPLASMS; PROSTAGLANDINS; PUBLIC OPINION; QUERCETIN; RECEPTORS; TESTOSTERONE; TUMOR CELLS