QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ju, Y. H. Articles by Helferich, W. G. Search for Related Content PubMed PubMed Citation Articles by Ju, Y. H. Articles by Helferich, W. G.

---

Nutrition and Cancer

ß-Sitosterol, ß-Sitosterol Glucoside, and a Mixture of ß-Sitosterol and ß-Sitosterol Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice¹

Young H. Ju², Laura M. Clausen^*, Kimberly F. Allred, Anthony L. Almada^** and William G. Helferich

Department of Food Science and Human Nutrition and ^* Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Physiology, University of Kentucky, Lexington, KY 40536; and ^** IMAGINutrition and MetaResponse Science, Laguna Niguel, CA 92677

²To whom correspondence should be addressed. E-mail: yhju{at}uiuc.edu.

We hypothesized that the phytosterols ß-sitosterol (BSS), ß-sitosterol glucoside (BSSG), and Moducare (MC; BSS:BSSG = 99:1) could modulate the growth of estrogen-dependent human breast cancer cells in vitro and in vivo. The present study evaluated the estrogenic and antiestrogenic effects of BSS, BSSG, and MC (0.001 to 150 µmol/L) on the proliferation of Michigan Cancer Foundation 7 (MCF-7) cells in vitro. Both BSS (>1 µmol/L) and MC (>50 µmol/L) increased MCF-7 cell proliferation. Treatment with 150 µmol/L of BSS and MC increased cell growth by 2.4 and 1.5 times, respectively, compared to the negative control (NC) group. However, BSSG had no effect at the concentrations tested. The effects of dietary BSS, BSSG, and MC on the growth of MCF-7 cells implanted in ovariectomized athymic mice were also evaluated. Estrogenic effects of the phytosterols were evaluated in the NC, BSS, BSSG, and MC treatment groups, and antiestrogenic effects were evaluated in the 17ß-estradiol (E₂), E₂ + BSS, E₂ + BSSG, and E₂ + MC treatment groups. Mice were treated with dietary BSS (9.8 g/kg AIN93G diet), BSSG (0.2 g/kg diet), or MC (10.0 g/kg diet) for 11 wk. Dietary BSS, BSSG, and MC did not stimulate MCF-7 tumor growth. However, dietary BSS, BSSG, and MC reduced E₂-induced MCF-7 tumor growth by 38.9% (P < 0.05), 31.6% (P = 0.08), and 42.13% (P < 0.05), respectively. The dietary phytosterols lowered serum E₂ levels by 35.1, 30.2, and 36.5% in the E₂ + BSS, E₂ + BSSG, and E₂ + MC groups, respectively (P < 0.05), compared to that of the E₂ treatment group. Estrogen-responsive pS2 mRNA expression in tumors did not differ among groups, but expression of the antiapoptotic marker B-cell lymphoma/leukemia-2 (bcl-2) in tumors from the E₂ + MC group was downregulated, compared to that of the E₂ treatment group. In summary, BSS and MC stimulated MCF-7 cell growth in vitro. Although BSSG comprises only 1% of MC, BSSG made MC less estrogenic than BSS alone in vitro. However, dietary BSS and MC protected against E₂-stimulated MCF-7 tumor growth and lowered circulating E₂ levels.

KEY WORDS: • ß-sitosterol • ß-sitosterol glucoside • breast cancer • MCF-7 cells

This article has been cited by other articles:

				M. Messina, W. McCaskill-Stevens, and J. W. Lampe Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst, September 20, 2006; 98(18): 1275 - 1284. [Abstract] [Full Text] [PDF]

				Y. H. Ju, K. F. Allred, C. D. Allred, and W. G. Helferich Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations Carcinogenesis, June 1, 2006; 27(6): 1292 - 1299. [Abstract] [Full Text] [PDF]

				Y. H. Ju, J. Fultz, K. F. Allred, D. R. Doerge, and W. G. Helferich Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice Carcinogenesis, April 1, 2006; 27(4): 856 - 863. [Abstract] [Full Text] [PDF]

				M. B. Schabath, L. M. Hernandez, X. Wu, P. C. Pillow, and M. R. Spitz Dietary Phytoestrogens and Lung Cancer Risk JAMA, September 28, 2005; 294(12): 1493 - 1504. [Abstract] [Full Text] [PDF]