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}

}