title: The antiproliferative and apoptotic effects of apigenin on glioblastoma cells.
abstract: OBJECTIVE
  Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM.
  
  
  METHODS
  Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses.
  
  
  RESULTS
  Our results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL.
  
  
  CONCLUSIONS
  Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Stump
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Santee
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Williams
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Kunze
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Chelsae E
authors.initials: CE
authors.lastname: Heinze
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Huseman
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gryka
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Simpson
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
authors.forename: Samson
authors.identifier: http://orcid.org/0000-0003-2780-2276
authors.initials: S
authors.lastname: Amos
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047310:Apigenin; C512478:EGFR protein, human; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases
keywords: apigenin; apoptosis; epidermal growth factor receptor; glioblastoma; proliferation