Conjugated linoleic acids (CLA), naturally found in dairy products and ruminant meat, are positional and geometric isomers (trans: t or cis: c) of
linoleic acid, and have been widely reported to possess anti-tumoral activity against
breast cancer both in vitro and in vivo. CLA isomer t9,t11 was recently proposed as an agonist of the transcriptional factor LXR, which is known for inducing genes implicated in
cholesterol efflux. In this study, the growth inhibitory effect of three CLA isomers (c9,t11-CLA, t9,t11-CLA and t10,c12-CLA) was investigated on MCF-7
breast cancer cells, as well as their effect on LXR target genes. Our results revealed that t9,t11-CLA was the most efficient isomer by decreasing MCF-7 proliferation, inhibiting migration, and inducing apoptosis after 24h of treatment. t9,t11-CLA treatment led to an increase in the
mRNA levels of LXR target genes involved in
cholesterol efflux (ABCG1 and ARL7), as well as an increase of
HMG-CoA-reductase which is the rate-limiting step of
cholesterol biosynthesis. Interestingly, confocal microscopy analysis showed that t9,t11-CLA treatment remarkably reduced the intracellular and membrane-associated
cholesterol levels. LXR activation through t9,t11-CLA isomer could lead to
cholesterol cell deprivation by stimulating its efflux, which results in the inhibition of cell proliferation and stimulation of apoptosis.