title: Differing Mechanisms of Death Induction by Fluorinated Taxane SB-T-12854 in Breast Cancer Cells.
abstract: Classical taxanes are routinely used in cancer therapy. In this study, mechanisms involved in death induction by the novel fluorine-containing taxane SB-T-12854 were investigated.
  
  
  
  We employed breast cancer SK-BR-3, MCF-7 and T47D cell lines to assess activation of individual caspases, changes in the expression of proteins of the Bcl-2 family, and the release of pro-apoptotic factors from mitochondria into the cytosol after SB-T-12854 treatment.
  
  
  
  Caspase-2, -8, and -9 were activated in SK-BR-3 and MCF-7 cells. Only caspase-8 was activated in T47D cells. Caspase-7 and -6 were activated in all tested cells while caspase-3 was activated only in SK-BR-3 cells. Pro-apoptotic Bad protein seems to be important for cell death induction in all tested cells. Anti-apoptotic Bcl-2 and pro-apoptotic Bim, Bok, Bid and Bik seem to be also associated with cell death induction in some of the tested cells. The mitochondrial apoptotic pathway was significantly activated in association with the release of cytochrome c and Smac from mitochondria, but only in SK-BR-3 cells, not in MCF-7 and T47D cells.
  
  
  
  Cell death induced by SB-T-12854, in the tested breast cancer cells, differs regarding activation of caspases, changes in levels of pro-apoptotic and anti-apoptotic proteins of the Bcl-2 family and activation of the mitochondrial apoptotic pathway.
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Jelinek
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Adela
authors.initials: A
authors.lastname: Kabelova
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sramek
authors.affiliation: Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, U.S.A.
authors.forename: Joshua
authors.initials: J
authors.lastname: Seitz
authors.affiliation: Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, U.S.A.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic jan.kovar@lf3.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Kovar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D006845:Hydrocarbons, Fluorinated; D043823:Taxoids; D020169:Caspases
keywords: Bcl-2 proteins; SB-T-12854; breast cancer cells; caspases; cytochrome c release