Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme.

Background: Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Materials and methods: Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPAR gamma mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPAR gamma in the anti-neoplastic activity of icaritin, PPAR gamma antagonist GW9662 or PPAR gamma siRNA was used. The activity of PPAR gamma was determined by DNA binding and luciferase assays. Results: Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPAR gamma played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPAR gamma. Conclusion: Our results suggest the PPAR gamma may mediate anti-neoplastic activities against GBM.