Latest Publications

@article{vondalova_blanarova_cisplatin_2011,

title = {Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway.},

author = {Olga Vondálová Blanárová and Iva Jelínková and Arpád Szöor and Belma Skender and Karel Soucek and Viktor Horváth and Alena Vaculová and Ladislav Andera and Petr Sova and János Szöllosi and Jirina Hofmanová and György Vereb and Alois Kozubík},

doi = {10.1093/carcin/bgq220},

issn = {1460-2180 0143-3334},

year  = {2011},

date = {2011-01-01},

journal = {Carcinogenesis},

volume = {32},

number = {1},

pages = {42–51},

abstract = {TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin.},

note = {Place: England},

keywords = {Amantadine/*analogs & derivatives/pharmacology, Apoptosis/*drug effects/physiology, Blotting, Cell Line, Cell Separation, Cisplatin/*pharmacology, Confocal, Flow Cytometry, Fluorescent Antibody Technique, Humans, Microscopy, Neoplasms/*metabolism, Organoplatinum Compounds/*pharmacology, Protein Transport/drug effects, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Signal Transduction/*drug effects/physiology, TNF-Related Apoptosis-Inducing Ligand/*metabolism, TNF-Related Apoptosis-Inducing Ligand/metabolism, Tumor, Western},

pubstate = {published},

tppubtype = {article}

}

@article{prochazkova_monocytic_2009,

title = {Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery.},

author = {Jirina Procházková and Lenka Stixová and Karel Soucek and Jirina Hofmanová and Alois Kozubík},

doi = {10.1111/j.1600-0609.2009.01240.x},

issn = {1600-0609 0902-4441},

year  = {2009},

date = {2009-07-01},

journal = {European journal of haematology},

volume = {83},

number = {1},

pages = {35–47},

abstract = {The block of hematopoietic differentiation program in acute myeloid leukemia cells can be overcome by differentiating agent like retinoic acid, but it has several side effects. A study of other differentiation signaling pathways is therefore useful to predict potential targets of anti-leukemic therapy. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-alpha (TNF-alpha) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 microm) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of mitogen-activated protein kinases (MAPKs) (p38, c-Jun amino-terminal kinase [JNK], extracellular signal-regulated kinase [ERK]), so we assessed their role in differentiation using appropriate pharmacologic inhibitors. The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-alpha co-treatment. On the other hand, down-regulation of pro-survival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-alpha. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. To conclude, we evidenced that the activation of apoptotic processes and pathways supporting apoptosis (p38 and JNK MAPKs) is required for the monocytic differentiation of HL-60 cells.},

note = {Place: England},

keywords = {Acute/*drug therapy/metabolism/*pathology, Amino Acid Chloromethyl Ketones/pharmacology, Apoptosis/*drug effects/physiology, Caspase Inhibitors, Caspases/metabolism, Cell Differentiation/drug effects, Cysteine Proteinase Inhibitors/pharmacology, Enzyme Activation/drug effects, HL-60 Cells, Humans, Indoles/*pharmacology, Leukemia, Lipoxygenase Inhibitors/pharmacology, MAP Kinase Signaling System/drug effects, Monocytes/*drug effects/pathology, NF-kappa B/antagonists & inhibitors, Promyelocytic, Tumor Necrosis Factor-alpha/*pharmacology},

pubstate = {published},

tppubtype = {article}

}

@article{soucek_transforming_2006,

title = {Transforming growth factor-beta1 inhibits all-trans retinoic acid-induced apoptosis.},

author = {Karel Soucek and Jirí Pacherník and Lukás Kubala and Jan Vondrácek and Jirina Hofmanová and Alois Kozubík},

doi = {10.1016/j.leukres.2005.09.007},

issn = {0145-2126},

year  = {2006},

date = {2006-05-01},

journal = {Leukemia research},

volume = {30},

number = {5},

pages = {607–623},

abstract = {The interaction between retinoids and transforming growth factor-beta1 (TGF-beta1) leading to regulation of proliferation, differentiation and apoptosis is not still fully understood. In this study, we demonstrated that a combination treatment with all-trans retinoic acid (ATRA) and TGF-beta1 led to the enhancement of ATRA-induced suppression of cell proliferation, which is accompanied by inhibition of ATRA-induced apoptosis in human leukemia HL-60 cells. This effect was preceded by the arrest of cells in G0/G1 cell cycle phase linked with pRb protein dephosphorylation, continuous accumulation of p21 and transiently increased level of p27, inhibitors of cyclin-dependent kinases. Inhibition of ATRA-induced apoptosis by TGF-beta1 was associated with an increased level of Mcl-1 protein, an anti-apoptotic member of Bcl-2 family, but not with inhibition of mitochondrial membrane depolarization. Levels of other Bcl-2 family proteins (Bcl-2, Bcl-X(L), Bad, Bak, Bax) were unaffected by simultaneous ATRA and TGF-beta1 treatment, when compared to ATRA alone. Upregulation of c-FLIP(L) protein, an inhibitor of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), correspond with inhibition of ATRA-induced (autocrine TRAIL-mediated) caspase-8 activation and apoptosis. These results suggest that apoptosis inhibition associated with proliferation block could depend on modulation of the TRAIL apoptotic pathway and regulation of the Mcl-1 protein level. In summary, we demonstrate that the balance of processes leading to regulation of proliferation and differentiation of myeloid cells can modulate cell sensitivity to apoptosis-inducing stimuli.},

note = {Place: England},

keywords = {Apoptosis Regulatory Proteins/metabolism/pharmacology, Apoptosis/*drug effects/physiology, bcl-2-Associated X Protein/drug effects/metabolism, CASP8 and FADD-Like Apoptosis Regulating Protein, Caspase 3, Caspase 8, Caspases/drug effects/metabolism, CD11b Antigen/biosynthesis/drug effects, Cell Cycle/drug effects, Cell Differentiation/drug effects, Cell Proliferation/drug effects, Cell Survival/drug effects, Cultured, Cyclin-Dependent Kinase Inhibitor p21/biosynthesis/drug effects, Drug Synergism, Enzyme Activation/drug effects, G1 Phase/drug effects, Granulocytes/drug effects/physiology, HL-60 Cells, Humans, Intracellular Signaling Peptides and Proteins/drug effects/metabolism, Membrane Glycoproteins/metabolism/pharmacology, Mitochondrial Membranes/drug effects/physiology, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/drug effects/metabolism, Phosphorylation, Proto-Oncogene Proteins c-bcl-2/drug effects/metabolism, Reactive Oxygen Species/metabolism, Resting Phase, Retinoblastoma Protein/drug effects/metabolism, TNF-Related Apoptosis-Inducing Ligand, Transforming Growth Factor beta/*pharmacology, Transforming Growth Factor beta1, Tretinoin/*antagonists & inhibitors/pharmacology, Tumor Cells, Tumor Necrosis Factor-alpha/metabolism/pharmacology},

pubstate = {published},

tppubtype = {article}

}

@article{vaculova_ethanol_2004,

title = {Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL-induced apoptosis.},

author = {Alena Vaculová and Jirina Hofmanová and Karel Soucek and Ladislav Andera and Alois Kozubík},

doi = {10.1016/j.febslet.2004.10.013},

issn = {0014-5793},

year  = {2004},

date = {2004-11-01},

journal = {FEBS letters},

volume = {577},

number = {1-2},

pages = {309–313},

abstract = {Identification of mechanisms of modulation of the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is important for its potential use in anticancer therapy. Ethanol can induce cell death in vitro and in vivo by different signalling pathways. Its effect in combination with death ligands is unknown. We investigated how ethanol modulates the effects of TRAIL in colon cancer cells. After combined TRAIL and ethanol treatment, a potentiation of caspase-8, -9, -3 activation, a proapoptotic Bid protein cleavage, a decrease of mitochondrial membrane potential, a complete poly(ADP)ribose polymerase cleavage, and disappearance of antiapoptotic Mcl-1 protein were demonstrated. Ethanol acts as a potent agent sensitizing colon cancer cells to TRAIL-induced apoptosis.},

note = {Place: England},

keywords = {Apoptosis Regulatory Proteins, Apoptosis/*drug effects/physiology, BH3 Interacting Domain Death Agonist Protein, Blotting, Carrier Proteins/metabolism, Caspases/metabolism, Colonic Neoplasms/enzymology/metabolism/*pathology, Ethanol/*pharmacology, HT29 Cells, Humans, Membrane Glycoproteins/*physiology, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/metabolism, Proto-Oncogene Proteins c-bcl-2/metabolism, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha/*physiology, Western},

pubstate = {published},

tppubtype = {article}

}