Induction of apoptosis and inhibition of NF-kappa B activation in human prostate cancer cells by the cis-9, trans-11 but not the trans-10, cis-12 isomer of conjugated linoleic acid

H J Song, Alan Arthur Sneddon, Steven Darryll Heys, K W J Wahle

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND. Conjugated linoleic acids (CLAs) have anti-tumorigenic properties in animal models and anti-proliferative effects on cancer cells in vitro. Previous studies have shown that the NF-kappa B pathway is involved regulating anti-apoptotic gene expression. The present study investigated the effects of CLAs (cis-9, trans-11, and trans-10, cis-12 isomers and a 50:50 mixture) on apoptosis and NF-kappa B activation in LNCaP cells.
METHODS. Apoptosis was assessed by annexin V staining using flow cytometry. TNF-alpha-induced NF-kappa B activity was determined by gel shift and reporter gene assays in addition to monitoring I kappa B alpha phosphorylation.
RESULTS. Only the CLA cis-9, trans-11 isomer significantly increased TNF-alpha-induced apoptosis (by 59%), which correlated with a reduction in NF-kappa B transcriptional activity (by 35%, P < 0.05), NF-kappa B binding activity (by 15%, P < 0.05), and phosphorylation of I kappa B alpha (by 36%, P < 0.01).
CONCLUSIONS. Our results may offer a mechanistic explanation for the reported inhibition of prostate tumor growth by CLAs in animal models of disease.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalThe Prostate
Volume66
Issue number8
Early online date20 Feb 2006
DOIs
Publication statusPublished - 1 Jun 2006

Keywords

  • conjugated linoleic acids
  • apoptosis
  • NF-kappa B
  • I kappa B phosphorylation
  • prostate cancer cells
  • protein-kinase-C
  • mammary carcinogenesis
  • alpha
  • proliferation
  • isoforms
  • TNF
  • rat
  • involvement
  • survival
  • pathway

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