Article

Modulation of liver X receptor signaling as novel therapy for prostate cancer.

The Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, CIS W325F, Chicago, IL 60637, USA.
Journal of Biomedical Science (impact factor: 2.01). 10/2007; 14(5):543-53. DOI:10.1007/s11373-007-9160-8
Source: PubMed

ABSTRACT Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXR agonists are effective for treatment of murine models of atherosclerosis, diabetes, and Alzheimer's disease. Recently we observed that LXR agonists suppressed proliferation of prostate and breast cancer cells in vitro and treatment of mice with the LXR agonist T0901317 suppressed the growth of prostate tumor xenografts. LXR agonists appear to cause G1 cell cycle arrest in cells by reducing expression of Skp2 and inducing the accumulation of p27(Kip). T0901317 induced expression of ATP-binding cassette transporter A1 (ABCA1) and delayed the progression of androgen-dependent human prostate tumor xenografts towards androgen-independency in mice. Phytosterols, the plant equivalent of mammalian cholesterol, have recently been shown to be agonists for LXRs. beta-Sitosterol and campesterol, the two most common phytosterols, suppressed proliferation of prostate and breast cancer cells. The anticancer activity of phytosterols may be due to LXR signaling. This review examines the potential use of LXR signaling as a therapeutic target in prostate and other cancers.

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Keywords

agonists
 
androgen-dependent human prostate tumor xenografts
 
ATP-binding cassette transporter A1
 
breast cancer cells
 
common phytosterols
 
glucose homeostasis
 
Liver X receptors
 
LXR agonist T0901317 suppressed
 
LXR agonists
 
LXR agonists suppressed proliferation
 
LXR signaling
 
LXRs
 
mammalian cholesterol
 
murine models
 
plant equivalent
 
potential use
 
prostate tumor xenografts
 
review examines
 
suppressed proliferation
 
therapeutic target
 

Chih-Pin Chuu