Effects of human breast stromal cells on conjugated linoleic acid (CLA) modulated vascular endothelial growth factor-A (VEGF-A) expression in MCF-7 cells

Anticancer Res. 2005 Nov-Dec;25(6B):4061-8.

Abstract

Background: Conjugated linoleic acid (CLA), a naturally occurring compound found in ruminant dairy and beef products, has been shown to possess anti-cancer ability in vivo and in vitro. There are several CLA isomers in ruminant-produced food products, among which t10,c12-CLA and c9,t11-CLA are most potent. Vascular endothelial growth factor-A (VEGF-A) has been implicated as an angiogenesis-activating cytokine. Our previous results indicated that CLA induced suppression of VEGF-A in MCF-7 cells, which may be one of CLA's anticancer mechanisms.

Materials and methods: The effects of 10,c12-CLA and c9,t11-CLA on VEGF-A mRNA and protein expression in MCF-7 cells, which were co-cultured with human breast stromal cells isolated from breast tissues of surgical specimens of mammoplasty and breast cancer patients, were detected by RT-PCR and Western blot analysis.

Results: VEGF-A mRNA and protein expressions were significantly (p < 0.05) elevated in co-cultured MCF-7 cells in comparison with cultured MCF-7 cells alone. Normal human breast stromal cells contribute greater effects in increasing VEGF-A protein expression in MCF-7 cells. Both t10,c12-CLA and c9,t11-CLA significantly (p < 0.05) decreased VEGF-A mRNA and protein levels in co-cultured MCF-7 cells. t10,c12-CLA appeared to be the more active isomer than c9, t11-CLA.

Conclusion: The results indicate that dietary CLA might serve as a chemo-therapeutic agent in human breast cancers by down-regulating VEGF-A expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Communication / physiology*
  • Cell Line, Tumor
  • Coculture Techniques
  • Down-Regulation
  • Humans
  • Isomerism
  • Linoleic Acids, Conjugated / pharmacology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Stromal Cells / cytology*
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Biomarkers, Tumor
  • Linoleic Acids, Conjugated
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • cis-9, trans-11-conjugated linoleic acid
  • trans-10,cis-12-conjugated linoleic acid