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

Abstract
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.
AuthorsJennifer S Truan, Jian-Min Chen, Lilian U Thompson
JournalMolecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Issue 10 Pg. 1414-21 (Oct 2010) ISSN: 1613-4133 [Electronic] Germany
PMID20425756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Fatty Acids, Omega-3
  • Receptors, Estrogen
  • Estradiol
  • Linseed Oil
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Breast Neoplasms (blood, drug therapy, metabolism, pathology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Down-Regulation (drug effects)
  • ErbB Receptors (metabolism)
  • Estradiol (administration & dosage, blood)
  • Fatty Acids, Omega-3 (blood, metabolism)
  • Female
  • Flax (chemistry)
  • Humans
  • Linseed Oil (pharmacology, therapeutic use)
  • Mice
  • Mice, Nude
  • Phytotherapy
  • Premenopause (blood)
  • Receptor, ErbB-2 (metabolism)
  • Receptors, Estrogen (metabolism)
  • Signal Transduction (drug effects)
  • Tumor Burden (drug effects)
  • Xenograft Model Antitumor Assays

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