Latest Publications

@article{svobodova_aryl_2015,

title = {The aryl hydrocarbon receptor-dependent disruption of contact inhibition in rat liver WB-F344 epithelial cells is linked with induction of survivin, but not with inhibition of apoptosis.},

author = {Jana Svobodová and Markéta Kabátková and Lenka Šmerdová and Petra Brenerová and Zdeněk Dvořák and Miroslav Machala and Jan Vondráček},

doi = {10.1016/j.tox.2015.04.001},

issn = {1879-3185 0300-483X},

year  = {2015},

date = {2015-07-01},

journal = {Toxicology},

volume = {333},

pages = {37–44},

abstract = {Inhibition of apoptosis by the ligands of the aryl hydrocarbon receptor (AhR) has been proposed to play a role in their tumor promoting effects on liver parenchymal cells. However, little is presently known about the impact of toxic AhR ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on apoptosis in other liver cell types, such as in liver epithelial/progenitor cells. In the present study, we focused on the effects of TCDD on apoptosis regulation in a model of liver progenitor cells, rat WB-F344 cell line, during the TCDD-elicited release from contact inhibition. The stimulation of cell proliferation in this cell line was associated with deregulated expression of a number of genes known to be under transcriptional control of the Hippo signaling pathway, a principal regulatory pathway involved in contact inhibition of cell proliferation. Interestingly, we found that mRNA and protein levels of survivin, a known Hippo target, which plays a role both in cell division and inhibition of apoptosis, were significantly up-regulated in rat liver epithelial cell model, as well as in undifferentiated human liver HepaRG cells. Using the short interfering RNA-mediated knockdown, we confirmed that survivin plays a central role in cell division of WB-F344 cells. When evaluating the effects of TCDD on apoptosis induction by camptothecin, a genotoxic topoisomerase I inhibitor, we observed that the pre-treatment of WB-F344 cells with TCDD increased number of cells with apoptotic nuclear morphology, and it potentiated cleavage of both caspase-3 and poly(ADP-ribose) polymerase I. This indicated that despite the observed up-regulation of survivin, apoptosis induced by the genotoxin was potentiated in the model of rat liver progenitor cells. The present results indicate that, unlike in hepatocytes, AhR agonists may not prevent induction of apoptosis elicited by DNA-damaging agents in a model of rat liver progenitor cells.},

note = {Place: Ireland},

keywords = {AhR, Animals, Apoptosis, Apoptosis/*drug effects, Aryl Hydrocarbon/*agonists/metabolism, Basic Helix-Loop-Helix Transcription Factors/*agonists/metabolism, BIRC5/survivin, Camptothecin/*toxicity, Caspase 3/metabolism, Cell Line, Contact inhibition, Contact Inhibition/*drug effects, Epithelial Cells/*drug effects/metabolism/pathology, Genetic/drug effects, Hippo signaling, Humans, Inbred F344, Inhibitor of Apoptosis Proteins/genetics/metabolism, Liver/*drug effects/metabolism/pathology, Microtubule-Associated Proteins/genetics/*metabolism, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases/metabolism, Polychlorinated Dibenzodioxins/*toxicity, Rats, Receptors, RNA Interference, Signal Transduction/drug effects, Survivin, TCDD, Time Factors, Topoisomerase I Inhibitors/*toxicity, Transcription, Transfection, Up-Regulation},

pubstate = {published},

tppubtype = {article}

}

@article{vaculova_different_2006,

title = {Different modulation of TRAIL-induced apoptosis by inhibition of pro-survival pathways in TRAIL-sensitive and TRAIL-resistant colon cancer cells.},

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

doi = {10.1016/j.febslet.2006.11.004},

issn = {0014-5793},

year  = {2006},

date = {2006-12-01},

journal = {FEBS letters},

volume = {580},

number = {28-29},

pages = {6565–6569},

abstract = {Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3beta.},

note = {Place: England},

keywords = {Apoptosis/*drug effects, Caspase 8/metabolism, Cell Survival/drug effects, Colonic Neoplasms/*pathology, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors, Glycogen Synthase Kinase 3 beta, Glycogen Synthase Kinase 3/metabolism, HT29 Cells, Humans, Keratin-18/metabolism, Mitogen-Activated Protein Kinase 1/antagonists & inhibitors, Mitogen-Activated Protein Kinase 3/antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/metabolism, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation/drug effects, Poly(ADP-ribose) Polymerases/metabolism, Proto-Oncogene Proteins c-akt/antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2/metabolism, TNF-Related Apoptosis-Inducing Ligand/*pharmacology},

pubstate = {published},

tppubtype = {article}

}

@article{horvath_platinumiv_2006,

title = {Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells.},

author = {Viktor Horváth and Olga Blanárová and Lenka Svihálková-Sindlerová and Karel Soucek and Jirina Hofmanová and Petr Sova and Ales Kroutil and Peter Fedorocko and Alois Kozubík},

doi = {10.1016/j.ygyno.2005.11.016},

issn = {0090-8258},

year  = {2006},

date = {2006-07-01},

journal = {Gynecologic oncology},

volume = {102},

number = {1},

pages = {32–40},

abstract = {OBJECTIVES: The resistance of tumor cells to cisplatin remains a major cause of treatment failure in cancer patients. In this study, the ability of Pt(IV) complex with adamantylamine-LA-12 and its reduced counterpart with lower oxidation state Pt(II)-LA-9 to overcome intrinsic cisplatin resistance was investigated. METHODS: The ovarian adenocarcinoma SK-OV-3 cells were exposed to cisplatin, LA-9, or LA-12 for 72 h and the effects of drug concentrations that caused 10% or 50% inhibition of cell proliferation were determined. After 24-72 h of sustained exposure viability, apoptosis and inhibition of proliferation were analyzed. DNA synthesis and cell cycle analysis were performed simultaneously in order to determine the modulation of cell cycle after platinum complexes treatment. RESULTS: Lung Resistance-related Protein (LRP/MVP) was detected in SK-OV-3 cells but not in the other two ovarian cancer lines with different sensitivity to cisplatin. LRP/MVP overexpression may be an important factor contributing to intrinsic cisplatin resistance. Interestingly, Pt(IV) complex-LA-12 had approximately 2.7-fold lower IC(50) concentration than LA-9 or cisplatin in SK-OV-3 cells. Moreover, LA-12 caused persistent accumulation of cells in S-phase of the cell cycle while LA-9 and cisplatin treatment-induced S-phase arrest was transient and shifted to G(2)/M-phase at later intervals. Apoptosis seemed to be not the dominant type of cell death caused by such the derivatives, but it was the most intensive after LA-12 treatment. CONCLUSIONS: We found strong differences between effects of Pt(IV) complex-LA-12 and Pt(II) derivatives-LA-9 and cisplatin on cytokinetic parameters. Overall, LA-12 but not its reduced Pt(II) counterpart LA-9 is the compound effective in p53 null human ovarian cancer cells and it is able to overcome intrinsic cisplatin resistance in these cells.},

note = {Place: United States},

keywords = {Adenocarcinoma/*drug therapy/metabolism/pathology, Amantadine/administration & dosage/analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols/*pharmacology, Blotting, Cell Cycle/drug effects, Cell Growth Processes/drug effects, Cell Line, Cisplatin/administration & dosage, DNA, Drug resistance, Female, Humans, Neoplasm, Neoplasm Proteins/biosynthesis, Neoplasm/biosynthesis, Organoplatinum Compounds/administration & dosage/*pharmacology, Ovarian Neoplasms/*drug therapy/metabolism/pathology, Poly(ADP-ribose) Polymerases/metabolism, Tumor, Vault Ribonucleoprotein Particles/biosynthesis, Western},

pubstate = {published},

tppubtype = {article}

}