Euxanthone Suppresses the Proliferation, Migration and Invasion of Human Medulloblastoma Cells by Inhibiting the RANK/RANKL Pathway

Background:Euxanthone is a plant-based flavonoid that is mostly isolated from a Chinese medicinal plant, Polygala caudate. This study was designed to evaluate the anticancer effects of euxanthone against human medulloblastoma cells.Materials and Methods:Cell viability was evaluated by CCK-8 and EdU assays. Apoptotic cell percentage was determined by annexin V/PI assay. The mRNA expression was determined by qRT-PCR. Wound healing and transwell assays were used to assess cell migration and invasion.Results:The results revealed aberrant activation of RANK/RANKL pathway in human medulloblastoma tissues and cell lines. Euxanthone suppressed the proliferation of the D425 medulloblastoma cells with comparatively lower cytotoxic effects against the normal human cerebellar granule cells. The IC50 of euxanthone against the D425 cells was found to be 10 mu M. Interestingly, silencing of receptor activator of nuclear factor k beta (RANK) could also suppress the proliferation of the D425 cells via induction of apoptosis. Nonetheless, overexpression of RANK could abolish the cytotoxic effects of euxanthone on the D425 cells. Finally, wound-heal and transwell assay showed that euxanthone suppressed the migration and invasion of the D425 medulloblastoma cells.Conclusion:Collectively, the results revealed the anticancer effects of euxanthone against human medulloblastoma cells via RANK/RANKL pathway. These results suggest the potential of euxanthone as a lead molecule in the development of chemotherapy for medulloblastoma.