PMID- 16286461
OWN - NLM
STAT- MEDLINE
DCOM- 20060731
LR  - 20240109
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 27
IP  - 5
DP  - 2006 May
TI  - Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an 
      isomer specific manner.
PG  - 972-81
AB  - 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.
FAU - Lee, Seong-Ho
AU  - Lee SH
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Tennessee, Knoxville, TN 37996, USA.
FAU - Yamaguchi, Kiyoshi
AU  - Yamaguchi K
FAU - Kim, Jong-Sik
AU  - Kim JS
FAU - Eling, Thomas E
AU  - Eling TE
FAU - Safe, Stephen
AU  - Safe S
FAU - Park, Yeonhwa
AU  - Park Y
FAU - Baek, Seung Joon
AU  - Baek SJ
LA  - eng
GR  - ES011657/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051114
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (ATF3 protein, human)
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Cytokines)
RN  - 0 (GDF15 protein, human)
RN  - 0 (Growth Differentiation Factor 15)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Activating Transcription Factor 3/metabolism
MH  - Anticarcinogenic Agents/chemistry
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/metabolism
MH  - Cytokines/*metabolism
MH  - Flow Cytometry
MH  - Growth Differentiation Factor 15
MH  - Humans
MH  - Linoleic Acids, Conjugated/*pharmacology
MH  - Protein Isoforms
MH  - RNA, Small Interfering/metabolism
MH  - Transfection
EDAT- 2005/11/16 09:00
MHDA- 2006/08/01 09:00
CRDT- 2005/11/16 09:00
PHST- 2005/11/16 09:00 [pubmed]
PHST- 2006/08/01 09:00 [medline]
PHST- 2005/11/16 09:00 [entrez]
AID - bgi268 [pii]
AID - 10.1093/carcin/bgi268 [doi]
PST - ppublish
SO  - Carcinogenesis. 2006 May;27(5):972-81. doi: 10.1093/carcin/bgi268. Epub 2005 Nov 
      14.