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Carcinogenesis Advance Access originally published online on February 19, 2004
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Carcinogenesis, Vol. 25, No. 7, 1185-1191, July 2004
Carcinogenesis vol.25 no.7 © Oxford University Press 2004; all rights reserved.

ARTICLE

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

Julio J. Ochoa1,6, Andrew J. Farquharson2, Ian Grant2,3, L. E. Moffat4, Steven D. Heys5 and Klaus W. J. Wahle2,3

1 Institute of Nutrition and Food Technology, Department of Physiology, University of Granada, C/Ramón y Cajal 4, 18071, Granada, Spain, 2 Rowett Research Institute, Greenburn Road North, Bucksburn, Aberdeen AB21 9SB, Scotland, UK, 3 School of Life Sciences, Robert Gordon University, St Andrew Street, Aberdeen AB 25 1HG, Scotland, UK, 4 Department of Urology, Grampian Universities NHS Trust, Foresterhill, Aberdeen, Scotland, UK and 5 Department of Surgical and Nutritional Oncology, Aberdeen University Medical School, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK

6 To whom correspondence should be addressed Email: jjoh{at}ugr.es

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.


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