Journal Article

Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for <i>cis</i>-9, <i>trans</i>-11 and <i>trans</i>-10, <i>cis</i>-12 isomers

Julio J. Ochoa, Andrew J. Farquharson, Ian Grant, L. E. Moffat, Steven D. Heys and Klaus W. J. Wahle

in Carcinogenesis

Volume 25, issue 7, pages 1185-1191
Published in print July 2004 | ISSN: 0143-3334
Published online July 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh116
Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers

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The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21WAF/Cip1). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21WAF1/Cip1 mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

Keywords: CLA, conjugated linoleic acids; COX, cyclooxygenase; c9,t11 CLA, cis-9, trans-11 CLA; LOX-5, 5-lipoxygenase; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; t10,c12 CLA, trans-10, cis-12 CLA

Journal Article.  4867 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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