Inhibition of cell proliferation: a new role of liver X receptors

Abstract

Evaluation of: Kim KH, Lee GY, Kim JI, Ham M, Won Lee J, Kim JB: Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity. J. Lipid Res. 51(12), 3425–3433 (2010). The liver X receptor (LXR) is a ligand-activated transcription factor that regulates the expression of genes involved in reverse cholesterol transport fromperipheral tissues to the liver, its conversion to bile acids and biliary excretion. LXRs are activated by endogenous oxygenated cholesterol derivatives (oxysterols)and operate as sterol sensors protecting against cholesterol overload. It was observed that LXR agonists inhibit proliferation of many, but not all, examined cell lines by inducing cell cycle arrest at the G1/S phase. This effect does not result from increased cholesterol export and reduction of cell cholesterol content, but rather from LXR-induced stimulation of fatty acid synthase and the increase in lipogenesis. In addition, LXR agonists inhibit the expression of cyclin A and cdc25a tyrosine phosphatase, both being involved in cell cycle progression from the G1 to the S phase. These results suggest that LXR agonists might be useful as anticancer agents.

Keywords:

• cell cycle
• cell proliferation
• lipogenesis
• liver X receptor