Flaxseed oil reduces the growth of human breast tumors (MCF-7) at high levels of circulating estrogen.

January 1, 2010 Human Health and Nutrition Data 0 Comments

Flaxseed oil reduces the growth of human breast tumors (MCF-7) at high levels of circulating estrogen.

Year: 2010
Authors: Truan, J.S. Chen, J-M. Thompson, L.U.
Publication Name: Mol. Nutr. Food Res.
Publication Details: Vol 54; Pages 1414-1421.


Flaxseed (FS) has been shown to attenuate mammary tumorigenesis, possibly due to its high alpha-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 8wks. 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. (Author's Abstract)
Studies have consistently shown that, at low circulating E2 simulating post-menopause, FS and its oil and lignan components can reduce the growth of established estrogen receptor-positive (ER 1) human breast tumors (MCF-7), alone or combined with the breast cancer drug tamoxifen (TAM). Less work has been conducted on the effect of FS at high circulating E2 levels simulating pre-menopause. At high E2 levels, FS also reduced MCF-7 tumor growth through decreased cell proliferation, increased apoptosis and reduced angiogenesis through lowering of vascular endothelial growth factor (VEGF) expression. The objective of this study was to investigate whether FSO is a component contributing to the anti-cancer action of FS at high circulating levels of E2 by determining the effect of FSO on established MCF-7 tumor growth and its potential mechanisms of action, with greater focus on the growth factor-mediated signaling pathway.  In OVX athymic mice with high circulating E2 concentration simulating premenopause, the ALA-rich FSO is effective in attenuating the growth of ER1 MCF-7 tumors and was due to a significant reduction in cell proliferation and increase in apoptosis. To understand the potential mechanisms of these effects on tumor growth, various signaling proteins of the growth factor-mediated and angiogenesis pathways were analyzed. A reduction in tumor cell proliferation and HER2 expression was sees with FSO, and increased apoptosis following FS treatment. FSO is one component of FS that can exert a tumor-reducing effect both at high and low circulating E2 levels and the mechanisms include the downregulation of the growth factor-mediated signaling pathway. Mechanisms by which ALA may affect tumor growth include increased lipid peroxidation and reduced fatty acid synthase (FAS). The authors conclude that at high levels of E2, FSO and its high ALA content reduced MCF-7 breast tumor growth by reducing cell proliferation and increasing apoptosis through modulation of the growth factor-mediated signaling pathway, and may in part account for the anti-cancer effect of FS. The results also suggest that ALA-rich FSO may potentially be consumed as an alternative to FS. Clinical trials need to be conducted before a more definitive recommendation can be given regarding the use of FSO and FS. (Editor's Comments)


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