Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXR? subcellular localization.

ABSTRACT: Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXR?-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXR?. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXR? with the truncated form of RXR? (t-RXR?) was responsible for the sequestration of LXR? in the cytoplasm in colon cancer cells. Moreover t-RXR? was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXR? and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXR?, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXR? could be a promising target in cancer therapy.

SUBMITTER: Courtaut F 

PROVIDER: S-EPMC4694942 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature