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

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Yongji Liu, Ling Shi, Yuan Liu, Peng Li, Guoping Jiang, Xiaoning Gao, Yongbin Zhang, Chuanwu Jiang, Weiping Zhu, Hongxing Han, Fang Ju
BackgroundGlioblastoma 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 methodsCell 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 PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays.ResultsOur 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 PPARγ 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 PPARγ.ConclusionOur results suggest the PPARγ may mediate anti-neoplastic activities against GBM.

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