Induction of apoptosis and inhibition of NF-κB activation in human prostate cancer cells by the cis-9, trans-11 but not the trans-10, cis-12 isomer of conjugated linoleic acid
被引:29
作者:
Song, Hyun-Ju
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机构:Robert Gordon Univ, Sch Life Sci, Aberdeen AB25 1HG, Scotland
Song, Hyun-Ju
Sneddon, Alan A.
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机构:Robert Gordon Univ, Sch Life Sci, Aberdeen AB25 1HG, Scotland
Sneddon, Alan A.
Heys, Steven D.
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机构:Robert Gordon Univ, Sch Life Sci, Aberdeen AB25 1HG, Scotland
Heys, Steven D.
Wahle, Klaus W. J.
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机构:Robert Gordon Univ, Sch Life Sci, Aberdeen AB25 1HG, Scotland
Wahle, Klaus W. J.
机构:
[1] Robert Gordon Univ, Sch Life Sci, Aberdeen AB25 1HG, Scotland
conjugated linoleic acids;
apoptosis;
NF-kappa B;
I kappa B phosphorylation;
prostate cancer cells;
D O I:
10.1002/pros.20351
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
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.