title: 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.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Truan
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Lilian U
authors.initials: LU
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism; D005260:Female; D019597:Flax / Q000737:chemistry; D006801:Humans; D008043:Linseed Oil / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D017697:Premenopause / Q000097:blood; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D066246:ErbB Receptors; D004958:Estradiol; D015525:Fatty Acids, Omega-3; D008043:Linseed Oil; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C512478:EGFR protein, human; C508053:ERBB2 protein, human