Project Description
The objective of this study was to determine the effect of flaxseed (FS) and its purified lignan precursor, secoisolariciresinol diglycoside (SDG), and oil (FO) components on the growth, recurrence and metastasis of estrogen receptor negative (ER-) human breast cancer cells, and some of the potential mechanisms involved. Athymic mice (immunodeficient mice) were injected with the ER- human breast cancer cells (MDA-MB 435) and fed with the basal diet (BD). In Experiment 1, when palpable tumours reached about 1 cm in diameter (at 8 weeks postcell injection), mice were randomly divided into five groups such that they have similar mean tumour size. They were then fed for 6 weeks either the BD (control) or the BD supplemented with 10% FS, SDG, FO or combined SDG and FO. The SDG and FO components were equivalent to the amounts in 10% FS. Their palpable tumour size were measured weekly. At necropsy, all tumours were excised and analyzed for indices of apoptosis, and cell proliferation. Some tumours in the BD and FS groups were also tested for extracellular vascular endothelial growth factor (VEGF) as an index of angiogenesis. In Experiment 2, the method was the same as in Experiment I except that the primary tumours at 8 weeks were excised prior to feeding the mice with the treatment diets. The incidence of palpable recurrent tumors were then noted weekly. In both experiments, the incidence and number of lung, lymph nodes and other organs metastatic tumors were examined. Experiment l showed that FS, FO and SDG+FO groups had lower tumor growth rate than the BD and SDG groups, but the SDG group did not differ from the BD group. AH treatment groups had lower metastasis incidence than the BD group but reached significance only in the FS and SDG+FO groups for lung metastasis, in the FO group for lymph node metastasis, in all treatments for other organ metastasis, and in the SDG+FO group for total metastasis. In experiment 2, compared with the BD group, the lung, lymph node and other organ metastasis incidence was reduced in all treatment groups, reaching significance in the SDG + FO groups for lung metastasis, the FS, FO and SDG + FO groups for lymph node metastasis, the FO group for the other organ metastasis, and the FS, FO, and SDG + FO groups for the total metastasis. No significant effect on recurrent tumour incidence was observed. The effect of flaxseed appears to be due to both its SDG and FO components, and the mechanisms include reducing tumour cell proliferation and angiogenesis and increasing apoptosis. It is concluded that flaxseed has the potential to reduce the growth and metastasis of established ER- human breast cancer.
