Document Detail


Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity.
MedLine Citation:
PMID:  20847297     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Liver X receptor (LXR), a sterol-activated nuclear hormone receptor, has been implicated in cholesterol and fatty acid homeostasis via regulation of reverse cholesterol transport and de novo fatty acid synthesis. LXR is also involved in immune responses, including anti-inflammatory action and T cell proliferation. In this study, we demonstrated that activated LXR suppresses cell cycle progression and proliferation in certain cell types. Stimulation of LXR with synthetic ligand T0901317 or GW3965 inhibited cell growth rate and arrested the cell cycle at the G1/S boundary in several cells, such as RWPE1, THP1, SNU16, LNCaP, and HepG2. However, LXR ligands did not exhibit antiproliferative activity in PC3, HEK293, or HeLa cells. Interestingly, activated LXR-mediated cell cycle arrest is closely correlated with the lipogenic gene expression and triacylglyceride accumulation. In accordance with these findings, suppression of FAS via small-interference RNA (siRNA) partially alleviated the antiproliferative effect of LXR activation in RWPE1 cells. Together, these data suggest that LXR activation with its ligands inhibits cell proliferation and induces G1/S arrest through elevated lipogenic activity, thus proposing a novel effect of activated LXR on cell cycle regulation.
Authors:
Kang Ho Kim; Gha Young Lee; Jong In Kim; Mira Ham; Joo Won Lee; Jae Bum Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-16
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-10     Completed Date:  2011-02-22     Revised Date:  2011-12-21    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3425-33     Citation Subset:  IM    
Affiliation:
Department of Biophysics and Chemical Biology, School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Benzoic Acids / pharmacology*
Benzylamines / pharmacology*
Cell Cycle / drug effects*
Cell Proliferation / drug effects*
Dose-Response Relationship, Drug
Fatty Acids / biosynthesis,  metabolism
Humans
Hydrocarbons, Fluorinated / pharmacology*
Ligands
Lipogenesis / drug effects*
Orphan Nuclear Receptors / agonists*,  metabolism*
Sulfonamides / pharmacology*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Benzoic Acids; 0/Benzylamines; 0/Fatty Acids; 0/GW 3965; 0/Hydrocarbons, Fluorinated; 0/Ligands; 0/Orphan Nuclear Receptors; 0/Sulfonamides; 0/TO-901317; 0/liver X receptor

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