Previous studies have shown that dietary flaxseed (FS) can reduce the growth of established human
breast tumors in athymic mice with low circulating
estrogen concentrations. In this study, we determined the effect of FS compared with pure
lignan at the level it is present in FS [
secoisolariciresinol diglucoside (SDG)] and to the
lignan-rich fraction [FS hull (FH)] on human
breast tumor growth and their potential mechanisms of action. Ovariectomized, athymic mice, each with an implanted
17 beta-estradiol (E2) pellet (0.36 mg), were injected with human
estrogen receptor (ER) positive
breast cancer cells (MCF-7). When
tumors were established, the E2 pellet was removed. Mice were fed either the control basal diet (BD), FS (100 g/kg diet), SDG (1 g/kg diet), or FH (18 g/kg diet) for 8 wk. Compared with the BD, FS and SDG significantly decreased the palpable
tumor size, but effects of FS, SDG, and FH did not differ from one another. All treatments significantly inhibited cell proliferation, but only FS and SDG induced significantly higher apoptosis. Both FS and SDG significantly decreased
mRNA expressions of Bcl2,
cyclin D1, pS2,
ERalpha, and
ERbeta,
epidermal growth factor receptor, and
insulin-like growth factor receptor. FS also reduced
human epidermal growth factor receptor 2 mRNA and SDG decreased phospho-specific
mitogen-activated protein kinase expression. FH did not significantly reduce these
biomarkers. In conclusion, pure SDG has a similar effect as FS in reducing
tumor growth and in mechanisms of action, including downregulating ER- and
growth factor-mediated cell signaling. The lesser effects of FH indicate a need for a higher dose to be more effective.