secoisolariciresinol-diglucoside and Weight-Gain

Secoisolariciresinol diglucoside (SDG) has positive effects on obesity and its complications. We investigated the effects and mechanism of SDG on high-fat and high-fructose diet (HFFD)-induced hepatic lipid metabolic disorders. Supplementation with 40 mg kg

Topics: Animals; Butylene Glycols; Calcium; Diet, High-Fat; Down-Regulation; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Energy Intake; Fatty Acids; Gene Expression Regulation; Glucosides; Hep G2 Cells; Humans; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondria; Palmitic Acid; Up-Regulation; Weight Gain

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.

Topics: Animal Feed; Animals; Breast Neoplasms; Butylene Glycols; Cell Line, Tumor; Energy Intake; Estradiol; Female; Flax; Glucosides; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Organ Size; Plant Extracts; Receptors, Estrogen; Seeds; Uterus; Weight Gain