Liver X receptor activation induces apoptosis of melanoma cell through caspase pathway

Abstract

Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated transcription factors regulating lipid metabolism and inflammation. Recent discoveries found LXRs could regulate tumor growth in a variety of cancer cell lines. In this study, we investigated the effect of LXR activation on melanoma cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10 and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317 induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner. Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317 on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6 mice. Altogether, this study demonstrates the critical role of LXRs in the regulation of melanoma growth and presents the LXR agonist T0901317 as a potential anti-melanoma agent.

Cholesterol and breast cancer pathophysiology

“…Further, there are data suggesting that this oxysterol can inhibit HMGCR activity in an indirect fashion, although the mechanism behind this activity is unclear [50]. Based on this established biology it was expected that 27HC would inhibit the growth of cancer cells, as has been observed for other LXR agonists [51–53]. However, recent studies have shown that 27HC actually promotes the proliferation of ER-positive breast cancer cell lines, in vitro [42, 54].…”

Liver X receptor agonist T0901317 reverses resistance of A549 human lung cancer cells to EGFR‐TKI treatment

“…LXR agonists can disrupt the proliferation of several cell types via altering expression levels of genes involved in controlling cell cycle and reduce angiogenesis in pathological conditions of uncontrolled angiogenesis . Recently, accumulating evidence indicates the important functional role of LXRs in a variety of malignancies, affecting both tumor growth and tumor metastasis . For example, the synthetic ligand T0901317 can inhibit prostate cancer cell proliferation and tumor formation and overexpression of LXRα can sensitize cancer cells to the ligand .…”

The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer

“…Whereas 27HC may have several functions within cells its role as an LXR agonist which inhibits cholesterol production and increases cholesterol efflux from cells is very well established. Thus, it would be expected, as has been observed for other LXR agonists, that 27HC would inhibit the growth of cancer cells (44-46). However, we and others have shown that 27HC actually promotes the proliferation of ER-positive, but not ER-negative, breast cancer cell lines in vitro (29) .…”