TY - JOUR T1 - LXR Agonists and ABCG1-dependent Cholesterol Efflux in MCF-7 Breast Cancer Cells: Relation to Proliferation and Apoptosis JF - Anticancer Research JO - Anticancer Res SP - 3007 LP - 3013 VL - 32 IS - 7 AU - ALI EL ROZ AU - JEAN-MARIE BARD AU - JEAN-MICHEL HUVELIN AU - HASSAN NAZIH Y1 - 2012/07/01 UR - http://ar.iiarjournals.org/content/32/7/3007.abstract N2 - Background: Liver X receptor (LXR) plays a key role in reverse cholesterol transport by inducing the expression of the ATP-binding cassette (ABC) transporters, implicated in cholesterol efflux. Recent data showed that LXR agonists inhibit the proliferation of multiple types of human cancer cells. However, whether these effects are related to cholesterol efflux has not yet been elucidated. Materials and Methods: Effects of two LXR agonists (TO901317 and 22(R)-hydroxycholesterol [22(R)-HC]) on proliferation, apoptosis and cholesterol efflux were examined in MCF-7 breast cancer cells. Results: Treatment with LXR agonists (TO901317 at 20 μM and 22(R)-HC at 2 μg/ml) inhibited proliferation and induced apoptosis of MCF-7 cells. Furthermore, LXR activation resulted in an increase in gene and protein levels of ABCG1 transporters and in cholesterol efflux to isolated high-density lipoprotein (HDL), without affecting the ABCA1/APOA-I mediated efflux. Under these conditions, a remarkable reduction of intracellular and membrane-associated cholesterol levels was observed. Conclusion: LXR activation in MCF-7 cells could deprive cells of cholesterol, required for their growth, by stimulating its efflux, resulting in the inhibition of cell proliferation and in stimulation of apoptosis. ER -