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The effect of secoisolariciresinol diglucoside and flaxseed oil, alone and in combination, on MCF-7 tumor growth and signaling pathways.

Abstract
Flaxseed (FS), an oilseed containing high amounts of the phytoestrogen lignan, secoisolariciresinol diglucoside (SDG), and n-3 fatty acid, alpha-linolenic acid-rich oil (FO), has been shown to inhibit the growth of established human breast tumors (MCF-7) in ovariectomized (OVX) athymic mice. However, the major FS component responsible for this effect and the mechanism(s) of its action are unclear. Hence, this study determined, in a 2 x 2 factorial design, the effect of SDG and FO, alone or in combination, on the growth of established human estrogen receptor positive (ER+) breast tumors and the potential mechanism(s) of its action. OVX mice with established ER+ human breast tumors (MCF-7) were treated for 8 wk with basal diet (BD, control) or BD supplemented with SDG (1 g/kg), FO (38.5 g/kg), or SDG + FO. All treatments reduced the tumor growth, but SDG had the greatest effect primarily through reducing tumor cell proliferation rather than increasing apoptosis. SDG had a main effect in the reduction of PS2, BCL2, and IGF-1R mRNA expression, whereas FO had a main effect only in PAKT reduction. SDG alone also lowered the ERalpha, ERbeta, EGFR, BCL2 mRNA, and PMAPK protein, indicating that its effect involves the modulation of the ER- and growth factor receptor-mediated signaling pathways.
AuthorsJasdeep Kaur Saggar, Jianmin Chen, Paul Corey, Lilian U Thompson
JournalNutrition and cancer (Nutr Cancer) Vol. 62 Issue 4 Pg. 533-42 ( 2010) ISSN: 1532-7914 [Electronic] United States
PMID20432175 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Butylene Glycols
  • Glucosides
  • Phytoestrogens
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Growth Factor
  • Linseed Oil
  • secoisolariciresinol diglucoside
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Biomarkers, Tumor (genetics, metabolism)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Butylene Glycols (pharmacology, therapeutic use)
  • Female
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Glucosides (pharmacology, therapeutic use)
  • Humans
  • Linseed Oil (pharmacokinetics, therapeutic use)
  • Mice
  • Mice, Nude
  • Phytoestrogens (pharmacology, therapeutic use)
  • Phytotherapy
  • Proto-Oncogene Proteins (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Receptors, Estrogen (genetics, metabolism)
  • Receptors, Growth Factor (genetics, metabolism)
  • Signal Transduction (drug effects)
  • Time Factors
  • Tumor Burden (drug effects)
  • Xenograft Model Antitumor Assays

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