Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner | Academic Article individual record
abstract

Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products, have anti-tumorigenic and pro-apoptotic properties in animal as well as in vitro models of cancer. However, the cellular mechanism has not been fully understood. NAG-1 (non-steroidal anti-inflammatory drug-activated gene-1) is induced by several dietary compounds and belongs to a TGF-beta superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. The present study was performed to elucidate the molecular mechanism by which CLA stimulates anti-tumorigenic activity in human colorectal cancer (CRC) cells. The trans-10, cis-12-CLA (t10,c12-CLA) repressed cell proliferation and induced apoptosis, whereas linoleic acid or c9,t11-CLA showed no effect on cell proliferation and apoptosis. We also found that t10,c12-CLA induced the expression of a pro-apoptotic gene, NAG-1, in human CRC cells. Inhibition of NAG-1 expression by small interference RNA (siRNA) results in repression of t10,c12-CLA-induced apoptosis. Microarray analysis using t10,c12-CLA-treated HCT-116 cells revealed that activating transcription factor 3 (ATF3) was induced and its expression was confirmed by western analysis. The t10,c12-CLA treatment followed by the overexpression of ATF3 increased NAG-1 promoter activity in HCT-116 cells. We further provide the evidence that t10,c12-CLA inhibited the phosphorylation of AKT and the blockage of GSK-3 by siRNA abolished t10,c12-CLA-induced ATF3 and NAG-1 expression. The current study demonstrates that t10,c12-CLA stimulates ATF3/NAG-1 expression and subsequently induces apoptosis in an isomer specific manner. These effects may be through inhibition of AKT/GSK-3beta pathway in human CRC cells.

authors
author list (cited authors)
Lee, S. H., Yamaguchi, K., Kim, J. S., Eling, T. E., Safe, S., Park, Y., & Baek, S. J.
publication date
2006
published in
keywords
  • Flow Cytometry
  • Linoleic Acids, Conjugated
  • Cytokines
  • Protein Isoforms
  • Humans
  • Colorectal Neoplasms
  • Activating Transcription Factor 3
  • Anticarcinogenic Agents
  • Apoptosis
  • Transfection
  • Cell Proliferation
  • Cell Line, Tumor
  • RNA, Small Interfering
  • Growth Differentiation Factor 15
citation count

101