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

43 Scopus citations

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

ASJC Scopus subject areas

  • Cancer Research

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  • 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