Arachidonic acid-induced gene expression in colon cancer cells

Arta M Monjazeb, Kevin P. High, Abbie Connoy, Lori S. Hart, Constantinos Koumenis, Floyd H. Chilton

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

It is well documented that arachidonic acid (AA) and its metabolites are intimately linked to cancer biology. However, the downstream mechanism(s) that link AA levels to cancer cell proliferation remain to be elucidated. Initial experiments in the current study showed that exogenous AA and inhibitors of AA metabolism that lead to the accumulation of unesterified AA are cytotoxic to the colon cancer cell line, HCT-116. Additionally, exogenous AA and triacsin C, an inhibitor of AA acylation, induced apoptosis and related caspase-3 activity in a transcriptionally dependent manner. Gene array analysis revealed that both exogenous AA and triacsin C alter the expression of similar genes in HCT-116 cells. For example, both downregulate several genes with well-documented roles in cell survival and apoptotic resistance. Conversely, both upregulate genes encoding activator protein-1 (AP-1) transcription factors, which have known roles in inducing apoptosis, and genes that counteract ras (Erk/MAPK) growth signaling pathways. Real-time polymerase chain reaction and immunoblotting demonstrated that mRNA and protein levels of one of the major AP-1 transcription factors, c-Jun, is markedly elevated by exogenous AA and triacsin C. Additionally, the cyclooxygenase inhibitor, sulindac sulfide, increases c-Jun mRNA levels. Together, these studies reveal that the generation of intracellular AA and its subsequent impact on gene expression probably represents a critical step that regulates colon cancer cell proliferation.

Original languageEnglish (US)
Pages (from-to)1950-1960
Number of pages11
JournalCarcinogenesis
Volume27
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

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Arachidonic Acid
Colonic Neoplasms
Gene Expression
Transcription Factor AP-1
Transcription Factors
Cell Proliferation
Apoptosis
Genes
HCT116 Cells
Messenger RNA
ras Genes
Cyclooxygenase Inhibitors
Acylation
Immunoblotting
Caspase 3
Real-Time Polymerase Chain Reaction
Neoplasms
Cell Survival
Up-Regulation
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research

Cite this

Monjazeb, A. M., High, K. P., Connoy, A., Hart, L. S., Koumenis, C., & Chilton, F. H. (2006). Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis, 27(10), 1950-1960. https://doi.org/10.1093/carcin/bgl023

Arachidonic acid-induced gene expression in colon cancer cells. / Monjazeb, Arta M; High, Kevin P.; Connoy, Abbie; Hart, Lori S.; Koumenis, Constantinos; Chilton, Floyd H.

In: Carcinogenesis, Vol. 27, No. 10, 10.2006, p. 1950-1960.

Research output: Contribution to journalArticle

Monjazeb, AM, High, KP, Connoy, A, Hart, LS, Koumenis, C & Chilton, FH 2006, 'Arachidonic acid-induced gene expression in colon cancer cells', Carcinogenesis, vol. 27, no. 10, pp. 1950-1960. https://doi.org/10.1093/carcin/bgl023
Monjazeb AM, High KP, Connoy A, Hart LS, Koumenis C, Chilton FH. Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-1960. https://doi.org/10.1093/carcin/bgl023
Monjazeb, Arta M ; High, Kevin P. ; Connoy, Abbie ; Hart, Lori S. ; Koumenis, Constantinos ; Chilton, Floyd H. / Arachidonic acid-induced gene expression in colon cancer cells. In: Carcinogenesis. 2006 ; Vol. 27, No. 10. pp. 1950-1960.
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