title: Flavopiridol's antiproliferative effects in glioblastoma multiforme.
abstract: OBJECTIVE
  Glioblastoma multiforme (GBM) is largely refractory to surgical operation, radiotherapy, and chemotherapy in use today. Remaining lifetime accounting for the GBM-affected patients varies between 12 and 16 months generally. The most frequently altered genes in GBM are p53, epidermal growth factor receptor, PTEN, and cyclin-dependent kinase inhibitor 2A. Our aim is to investigate the antiproliferative and apoptotic effects of flavopiridol, a cyclin-dependent kinases and specific phosphokinase inhibitor, on glioblastoma cell lines having different genetic profiles: U87MG, U118MG, and T98G.
  
  
  METHODS
  Cell viability and IC50 values were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, protein expressions were determined by Western blot and caspase activities were analyzed by activity kit.
  
  
  RESULTS
  Western blot analysis showed down-regulation of the cyclin D1, c-Myc, and p53 protein activities, and up-regulation of p27KIP1 activity after flavopiridol treatment. Additionally, flavopiridol diminished p-Akt protein levels generally which induces inhibition of proliferation.
  
  
  CONCLUSIONS
  The present study demonstrated that flavopiridol did not induce caspase-3/7 activation, BIM, and BAX pro-apoptotic proteins but it leads to the expression changes of various proteins that inhibit proliferation and eternity in glioblastoma cell lines which have different genetic alterations.
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Gozde
authors.initials: G
authors.lastname: Cobanoglu
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Ufuk University, Ankara, Turkey.
authors.forename: Irem Dogan
authors.initials: ID
authors.lastname: Turacli
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Ayla Cihan
authors.initials: AC
authors.lastname: Ozkan
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ekmekci
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C077990:alvocidib; D053148:Caspase 3; D053179:Caspase 7