1-2-dilauroylphosphatidylcholine and Glioblastoma

Nervous system malignancies are characterized by rapid progression and poor survival rates. These clinical observations underscore the need for novel therapeutic insights and pharmacological targets. To this end, here, we identify the orphan nuclear receptor NR5A2/LRH1 as a negative regulator of cancer cell proliferation and promising pharmacological target for nervous system-related tumors. In particular, clinical data from publicly available databases suggest that high expression levels of NR5A2 are associated with favorable prognosis in patients with glioblastoma and neuroblastoma tumors. Consistently, we experimentally show that NR5A2 is sufficient to strongly suppress proliferation of both human and mouse glioblastoma and neuroblastoma cells without inducing apoptosis. Moreover, short hairpin RNA-mediated knockdown of the basal expression levels of NR5A2 in glioblastoma cells promotes their cell cycle progression. The antiproliferative effect of NR5A2 is mediated by the transcriptional induction of negative regulators of the cell cycle,

Topics: Animals; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Glioblastoma; Humans; Kaplan-Meier Estimate; Mice, SCID; Nervous System Neoplasms; Neural Stem Cells; Neuroblastoma; Phosphatidylcholines; Receptors, Cytoplasmic and Nuclear; Xenograft Model Antitumor Assays