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

Abstract

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 (p21(WAF/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 p21(WAF1/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.

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

“…Importantly, our studies point to a critical role for Bcl-2 in mediating the apoptotic effects of CLA in TM4t cells. Previous Western blot studies indicated that t10,c12-CLA induced either a modest 20-25% loss, or no loss, of total cellular Bcl-2 protein in cultured colon, prostate or breast cancer cells [23,26,27]. However, using mitochondrial fractions, we found that t10,c12-CLA induced a marked concentrationdependent decrease of mitochondrial Bcl-2 after 3 days of treatment (10% of control levels relative to VDAC at 40 μM).…”

The inclusion of low quantities of lipids in the diet of ruminants fed low quality forages has little effect on rumen function

“…The common objectives in most studies using addition of FA in the diet, is to decrease saturated and trans FAs and increase conjugated linoleic acid (CLA)s, 18:3n-3, 20:5n-3, and 22:6n-3. These changes in FAs are related to human-health benefits (Ha et al, 1987;Ochoa et al, 2004), changes in the microbial population (Boeckaert et al, 2006), influences on animal metabolism (Bauman et al, 2011) or to enhancement of the overall performance of offspring, when fed to dams during pregnancy and lactation (Pickard et al, 2008;Or-Rashid et al, 2010). There are known differences between the FA profile of meat of grass fed animals and animals fed silage or concentrate-based diets (Poulson et al, 2004;Noci et al, 2005), but there is little information regarding the FA profile of cattle fed tropical grasses.…”

Comparison of two derivatisation methods for conjugated linoleic acid isomer analysis by Ag+‐HPLC/DAD in beef fat

“…1 shows a high repeatability value; however, both methods have low repeatability (but similar) values and low correlations for the trans-10,cis-12. This isomer attracts great interest with regards to its potential health effects, which include decreasing proliferation of prostate cancer cells, reducing overall body fat and enhancing body protein [25][26][27], as well as its potential detrimental effects, which include the promotion of colon carcinogenesis and the promotion of atherosclerosis [28,29]. This may be due to the small concentration of the trans-10,cis-12 isomer.…”