title: LXR agonists and ABCG1-dependent cholesterol efflux in MCF-7 breast cancer cells: relation to proliferation and apoptosis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: EA-2160, MMS, Mer, Molecules, Sante, IUML: Institut Universitaire Mer et Littoral FR3473 CNRS, Faculty of Pharmacy, Nantes, France.
authors: Ali
authors: A
authors: El Roz
authors: Jean-Marie
authors: JM
authors: Bard
authors: Jean-Michel
authors: JM
authors: Huvelin
authors: Hassan
authors: H
authors: Nazih
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D006888:Hydroxycholesterols; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C419353:ABCG1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C003585:22-hydroxycholesterol