title: The effect of quercetin and imperatorin on programmed cell death induction in T98G cells in vitro.
abstract: BACKGROUND
  High expression of HSP27 and HSP72 in glioma cells has been closely associated with chemoresistance and decreased sensitivity to programmed cell death induction. Therefore, it is important to devise therapies that effectively target invasive cancer cells by inducing cell death. The aim of our study was to assess the effect of quercetin and imperatorin applied separately and in combinations on the apoptosis and autophagy induction in human T98G cells cultured in vitro.
  
  
  METHODS
  Cell death induction was analyzed by the staining method. The Western blotting technique and fluorimetric measurements of activity were used to assess the expression of marker proteins of apoptosis and autophagy. The specific siRNA transfected method was used for blocking of the expression of HSP27 and HSP72 genes.
  
  
  RESULTS
  The experiments revealed the highest percentage of apoptotic cells after using a 50?M concentration of both compounds. Simultaneous quercetin and imperatorin administration induced apoptosis more effectively than incubation with single drugs. These results were accompanied with decreased HSP27 and HSP72 expression, and a high level of caspase-3 and caspase-9 activity. Autophagy was not observed. Additional experiments were performed on a cell line with blocked Hsp27 and Hsp72 expression and significant increase the sensitivity to apoptosis induction upon quercetin and imperatorin treatment was noticed.
  
  
  CONCLUSIONS
  The present study indicates that quercetin and imperatorin are potent apoptosis inducers, especially when they act synergistically, which may be a promising combination useful in glioma therapy. Our results also demonstrated that blocking the HSP27 and HSP72 gene expression might serve as a therapeutic target for the human brain cancer.
authors.affiliation: Department of Comparative Anatomy and Anthropology, Institute of Biology, Maria Curie-Sklodowska University, Lublin, Poland. Electronic address: dorota.badziul@wp.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Bądziul
authors.affiliation: Department of Comparative Anatomy and Anthropology, Institute of Biology, Maria Curie-Sklodowska University, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakubowicz-Gil
authors.affiliation: Department of Medical Biology, Institute of Agricultural Medicine, Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Langner
authors.affiliation: Department of Medical Biology, Institute of Agricultural Medicine, Lublin, Poland; Department of Immunology and Virology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
authors.affiliation: Department of Pharmacognosy with Medical Plant Unit, Medical University, Lublin, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Głowniak
authors.affiliation: Department of Comparative Anatomy and Anthropology, Institute of Biology, Maria Curie-Sklodowska University, Lublin, Poland.
authors.forename: Antoni
authors.initials: A
authors.lastname: Gawron
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D011564:Furocoumarins / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D011564:Furocoumarins; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011794:Quercetin; D020169:Caspases; C031534:imperatorin
keywords: Cell death; Glioblastoma; HSP; Imperatorin; Quercetin