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

Nutr Cancer. 2010;62(4):533-42. doi: 10.1080/01635580903532440.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Butylene Glycols / pharmacology*
  • Butylene Glycols / therapeutic use*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use*
  • Humans
  • Linseed Oil / pharmacokinetics*
  • Linseed Oil / therapeutic use
  • Mice
  • Mice, Nude
  • Phytoestrogens / pharmacology
  • Phytoestrogens / therapeutic use
  • Phytotherapy
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Signal Transduction / drug effects*
  • Time Factors
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Butylene Glycols
  • Glucosides
  • Phytoestrogens
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Growth Factor
  • Linseed Oil
  • secoisolariciresinol diglucoside