Lignans and tamoxifen, alone or in combination, reduce human breast cancer cell adhesion, invasion and migration in vitro.

Key Findings:

Previous studies have shown that flaxseed can inhibit the spontaneous metastasis of the estrogen receptor negative (ER−) human breast cancer MDA-MB-435 in nude mice and the experimental lung metastasis of murine melanoma B16BL6 cells in mice. The inhibition of growth and metastasis of ER− human breast cancer is associated with the reduction of expression of epidermal growth factor receptor (EGFR), insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) in the primary tumors. Tamoxifen (TAM) can block the breast (ER+ or ER−) or non-breast cancer metastatic cascade by inhibition of cell adhesion and invasion and alteration of cell migration. ED, EL, and TAM alone reduced cell adhesion, invasion and migration of two ER− breast cancer cell lines, MDA-MB-435 and MDA-MB-231, and in combination, they are antagonistic with anti-cancer effects. This study indicates that consumption of lignan-rich flaxseed by breast cancer patients taking TAM may be protective against metastasis.

ABSTRACT:

Flaxseed has been shown to reduce the metastasis of estrogen receptor negative (ER−) human breast cancer in nude mice. This study determined whether enterodiol (ED) and enterolactone (EL), metabolites of plant lignans exceptionally rich in flaxseed, and tamoxifen (TAM), alone or in combination, can influence the various steps of metastasis, that is, breast cancer cell adhesion, invasion and migration, of two ER− human breast cancer cell lines, MDA-MB-435 and MDA-MB-231. The inhibition by ED, EL or TAM (1–5μM) of cell adhesion to Matrigel or extracellular matrices, fibronectin, laminin, and type IV collagen, as well as cell invasion was dose dependent in both cell lines. When ED, EL and TAM were combined at 1μM, a greater inhibitory effect on cell adhesion and invasion was observed than with either compound alone. ED and EL at doses of 0.1–10μM reduced cell migration, but TAM had no effect at 0.1 and 1 μM, and exhibited a stimulatory effect at 10μM. It is concluded that lignans and TAM, alone or in combination, can inhibit the steps involved in the metastasis cascade. Although more investigations are required, the study also suggests that the intake of the lignan-rich flaxseed may not antagonize the effect of TAM in ER− breast cancer cells.