Flaxseed (FS) has been shown to attenuate mammary
tumorigenesis, possibly due to its high α-
linolenic acid (ALA)-rich oil (FSO) content. This study determined the effect of FSO on the growth of
estrogen receptor-positive human
breast tumors (MCF-7) in ovariectomized athymic mice at high premenopausal-like
estrogen (E2) levels. Mice with established MCF-7
tumors were fed basal diet (control) or basal diet supplemented with FSO (40 g/kg) for 8 wks. Compared with control, FSO reduced
tumor size (33%, p<0.05) and
tumor cell proliferation (38%, p<0.05) and increased apoptosis (110%, p<0.001). FSO also reduced human
epidermal growth factor receptor-2 (79%, p<0.05) and
epidermal growth factor receptor (57%, p=0.057) expression, which then may have led to a reduction in Akt (54%, p<0.05) and phosphorylation of
mitogen-activated protein kinase (MAPK) to phosphorylated MAPK (pMAPK, 28%, p<0.05).
Insulin-like growth factor-1 receptor,
vascular endothelial growth factor receptor, MAPK and phosphorylated Akt were not affected. FSO increased (p<0.001) serum ALA,
eicosapentaenoic acid and
docosahexaenoic acid and, in vitro, ALA reduced MCF-7 cell proliferation (33%, p<0.001). Thus, FSO regressed
estrogen receptor-positive human breast
tumorigenesis at high E2 levels via downregulation of the
growth factor mediated pathway, likely through its ALA content, and may explain the anti-tumorigenicity of FS.