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

Young H. Ju, Laura M. Clausen, Kimberly F. Allred, Anthony L. Almada, William G. Helferich

Research output: Contribution to journalArticlepeer-review

Abstract

We hypothesized that the phytosterols β-sitosterol (BSS), β-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 17β-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.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalJournal of Nutrition
Volume134
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Breast cancer
  • MCF-7 cells
  • β-sitosterol
  • β-sitosterol glucoside

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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