Modulation of liver X receptor signaling as novel therapy for prostate cancer.
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.
Chuu
Chih-Pin
CP
The Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, CIS W325F, Chicago, IL 60637, USA.
Kokontis
John M
JM
Hiipakka
Richard A
RA
Liao
Shutsung
S
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors; D006801:Humans; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear