Latest Publications

@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{vondracek_dimethyl_2006,

title = {Dimethyl sulfoxide potentiates death receptor-mediated apoptosis in the human myeloid leukemia U937 cell line through enhancement of mitochondrial membrane depolarization.},

author = {Jan Vondrácek and Karel Soucek and Michael A. Sheard and Katerina Chramostová and Zdenek Andrysík and Jirina Hofmanová and Alois Kozubík},

doi = {10.1016/j.leukres.2005.05.016},

issn = {0145-2126},

year  = {2006},

date = {2006-01-01},

journal = {Leukemia research},

volume = {30},

number = {1},

pages = {81–89},

abstract = {Dimethyl sulfoxide (DMSO) is a widely used prototypical chemical inducer of cell differentiation. In the present study, the effects of DMSO on susceptibility of human myeloid leukemia U937 cells towards ligation of distinct death receptors (DRs) were investigated. DMSO sensitized cells towards induction of apoptosis by anti-Fas antibody, tumour necrosis factor-alpha or Apo2 ligand/TNF-related apoptosis-inducing ligand (TRAIL). Apart from increasing Fas levels, DMSO did not affect expression of proteins in death signal transduction, such as Bcl-2 family proteins, FADD, caspase-3 and -8, the inhibitor of apoptosis proteins (IAPs) or cFLIP(L). However, DMSO significantly potentiated mitochondrial membrane depolarization, suggesting that this mechanism might be involved in sensitisation of myeloid cells to DR-mediated apoptosis.},

note = {Place: England},

keywords = {Adaptor Proteins, Apoptosis Regulatory Proteins/*metabolism, Apoptosis/*drug effects, CASP8 and FADD-Like Apoptosis Regulating Protein, Caspase 3, Caspase 8, Caspases/metabolism, Cryoprotective Agents/*pharmacology, Dimethyl Sulfoxide/*pharmacology, fas Receptor/*metabolism, Fas-Associated Death Domain Protein, Humans, Intracellular Signaling Peptides and Proteins, Leukemia, Membrane Glycoproteins/*metabolism, Mitochondria/metabolism/pathology, Mitochondrial Membranes/*metabolism/pathology, Myeloid/*metabolism/pathology, Proto-Oncogene Proteins c-bcl-2/metabolism, Signal Transducing/metabolism, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha/*metabolism, U937 Cells},

pubstate = {published},

tppubtype = {article}

}

@article{kovarikova_effects_2004,

title = {The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status.},

author = {Martina Kovaríková and Jirina Hofmanová and Karel Soucek and Alois Kozubík},

doi = {10.1111/j.1432-0436.2004.07201006.x},

issn = {0301-4681},

year  = {2004},

date = {2004-02-01},

journal = {Differentiation; research in biological diversity},

volume = {72},

number = {1},

pages = {23–31},

abstract = {The level of differentiation could influence sensitivity of colonic epithelial cells to various stimuli. In our study, the effects of TNF-alpha, inhibitors of arachidonic acid (AA) metabolism (baicalein, BA; indomethacin, INDO; niflumic acid, NA; nordihydroguaiaretic acid, NDGA), and/or their combinations on undifferentiated or sodium butyrate (NaBt)-differentiated human colon adenocarcinoma HT-29 cells were compared. NaBt-treated cells became growth arrested (blocked in G0/G1 phase of the cell cycle), and showed down-regulated Bcl-xL and up-regulated Bak proteins and increased expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). These cells were more perceptive to anti-proliferative and apoptotic effects of TNF-alpha. Both inhibitors of LOX (BA and NDGA) and COX (INDO and NA) in higher concentrations modulated cell cycle changes accompanying NaBt-induced differentiation and induced various level of cell death in undifferentiated and differentiated cells. Most important is our finding that TNF-alpha action on proliferation and cell death can be potentiated by co-treatment of cells with AA metabolism inhibitors, and that these effects were more significant in undifferentiated cells. TNF-alpha and INDO co-treatment was associated with accumulation of cells in G0/G1 cell cycle phase, increased reactive oxygen species production, and elevated caspase-3 activity. These results indicate the role of differentiation status in the sensitivity of HT-29 cells to the anti-proliferative and proapoptotic effects of TNF-alpha, AA metabolism inhibitors, and their combinations, and imply promising possibility for novel anti-cancer strategies.},

note = {Place: England},

keywords = {*Flavanones, Adenocarcinoma/drug therapy/pathology, Arachidonate 5-Lipoxygenase/metabolism, Arachidonic Acid/*metabolism, Butyrates/pharmacology, Caspase 3, Caspases/drug effects/metabolism, Cell Cycle/drug effects, Cell Differentiation/*drug effects, Cell Division/drug effects, Colonic Neoplasms/drug therapy/metabolism/pathology, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors/*pharmacology, Drug Synergism, Flavonoids/pharmacology, HT29 Cells/drug effects, Humans, Indomethacin/pharmacology, Isoenzymes/antagonists & inhibitors/metabolism, Lipoxygenase Inhibitors/*pharmacology, Masoprocol/pharmacology, Membrane Proteins, Niflumic Acid/pharmacology, Prostaglandin-Endoperoxide Synthases/metabolism, Tumor Necrosis Factor-alpha/*pharmacology},

pubstate = {published},

tppubtype = {article}

}

@article{vaculova_tumor_2002,

title = {Tumor necrosis factor-alpha induces apoptosis associated with poly(ADP-ribose) polymerase cleavage in HT-29 colon cancer cells.},

author = {Alena Vaculová and Jirina Hofmanova and Karel Soucek and Martina Kovariková and Alois Kozubík},

issn = {0250-7005},

year  = {2002},

date = {2002-06-01},

journal = {Anticancer research},

volume = {22},

number = {3},

pages = {1635–1639},

abstract = {BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known for its selective cytotoxic activity on tumour cells. We analysed the response of HT-29 human colon carcinoma cells to this cytokine. MATERIALS AND METHODS: After TNF-alpha treatment, cell proliferation, cell cycle, reactive oxygen species (ROS) production (flow cytometry), the amount of apoptotic cells (flow cytometry, fluorescence microscopy), cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 activity (Western blotting) were detected. RESULTS: TNF-alpha induced a decrease of cell growth and viability, an accumulation of cells in the S-phase of the cell cycle, an increase of subdiploid cell population and nuclear chromatin condensation and fragmentation, but not sooner than 96-120 hours. However, earlier events characteristic of apoptosis occurred, such as caspase-3 activation, PARP cleavage to 89 kDa fragment and changes in ROS production. CONCLUSION: We demonstrated that, in addition to being an early marker of apoptosis, activation of caspase-3 and degradation of PARP may play a causative role in HT-29 cell death induced by TNF-alpha.},

note = {Place: Greece},

keywords = {Apoptosis/*drug effects, Caspase 3, Caspases/metabolism, Cell Death/drug effects, Cell Division/drug effects, HT29 Cells/*drug effects/enzymology/pathology, Humans, Kinetics, Poly(ADP-ribose) Polymerases/*metabolism, Reactive Oxygen Species/metabolism, Tumor Necrosis Factor-alpha/*pharmacology},

pubstate = {published},

tppubtype = {article}

}