title: Icaritin induces apoptotic and autophagic cell death in human glioblastoma cells.
abstract: BACKGROUND
  GBM represents the most aggressive type of glioma which is featured by extremely aggressive invasion and destructive malignancy with a high proliferation rate. The aim of this study was to investigate the in vitro anti-tumor effect of icaritin in human GBM cell line U87.
  
  
  METHODS
  The effect of icaritin on In vitro cell viability was determined by MTT assay and colony formation assay. The inducing effect of icaritin on cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation was assessed by flow cytometry. The apoptotic cell death was also confirmed by TUNEL assay. The expression levels of target or marker molecules were examined by western blot. The activity of caspase-3, -8 and -9 was detected with ELISA kit.
  
  
  RESULTS
  Our results showed that icaritin significantly induced both caspase-dependent apoptosis and autophagy in human GBM cell line U87. Additionally, our findings revealed that icaritin exerted anti-tumor effect by modulating Stat3 through generating ROS and subsequent activation of AMPK and inhibition of mTOR. Further investigation also showed that icaritin-induced autophagy served as a pro-death function and possibly contributed to icaritin-induced apoptosis.
  
  
  CONCLUSIONS
  Icaritin potently inhibit the cell growth of human GBM cell line U87 through inducing both caspase-dependent apoptosis and autophagy. Base on our findings, icaritin can be considered as a promising candidate therapeutic agent for treatment of GBM, though further studies are needed.
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
authors.forename: Zhaopei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Meng
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jin
keywords: GBM; Icaritin; Stat3; apoptosis; autophagy