Dietary Flaxseed Inhibits Human Breast Cancer Growth and Metastasis and Down regulates Expression of Insulin-Like Growth Factor and Epidermal Growth Factor Receptor

Key Findings:

Previous studies showed that diet supplementation with flaxseed or its lignan SDG inhibits the initiation, promotion, and progression of mammary carcinogenesis in rats and can inhibit experimental metastasis of murine melanoma cells in mice. A reduction in plasma insulin like growth factor I (IGF-I) level and EGFR in breast cancer cells by flaxseed was shown. Flax reduced metastasis which could be due to a reduction in angiogenesis and/or proliferation. The flaxseed diet can reduce established ER negative breast cancer growth and inhibit its metastasis to the distant organs, particularly lymph node and lungs, and this inhibitory effect may be partly due to the down regulation of IGF-I and EGFR expression. This suggests a potential use of flaxseed in the treatment of advanced human breast cancer with ER-negative status.

ABSTRACT:

Recent studies indicate that diets rich in phytoestrogens and n-3 fatty acid have anticancer potential. This study determined the effect of flaxseed (FS), the richest source of lignans and ALA, on growth and metastasis of established human breast cancer in a nude mice model. Estrogen receptor-negative human breast cancer cells, MDA-MB-435, were injected into the mammary fat pad of mice (Ncr nu/nu) fed a basal diet (BD). At Week 8, mice were randomized into two diet groups, such that the groups had similar tumor size and body weight. One continued on the BD, while the other was changed to BD supplemented with 10% FS, until sacrifice at Week 15. A significant reduction (P < 0.05) in tumor growth rate and a 45% reduction (P = 0.08) in total incidence of metastasis were observed in the FS group. Lung metastasis incidence was 55.6% in the BD group and 22.2% in the FS group, while the lymph node metastasis incidence was 88.9% in the BD group and 33.3% in the FS group (P < 0.05). Mean tumor number (tumor load) of total and lymph node metastasis was significantly lower in the FS than in the BD group (P < 0.05). Metastatic lung tumor number was reduced by 82%, and a significantly lower tumor trend (P < 0.01) was observed in the FS group. Lung weight, which also reflects metastatic tumor load, in the FS group was reduced by 20% (P < 0.05) compared with the BD group. Immuno histo-chemical study showed that Ki-67 labeling index and expression of insulin-like growth factor I and epithelial growth factor receptor in the primary tumor were lower in the FS (P < 0.05) than in the BD group. In conclusion, flaxseed inhibited the established human breast cancer growth and metastasis in a nude mice model, and this effect is partly due to its down regulation of insulin-like growth factor I and epidermal growth factor receptor expression.