Latest Publications

@article{kauerova_ring-substituted_2020,

title = {Ring-Substituted 1-Hydroxynaphthalene-2-Carboxanilides Inhibit Proliferation and Trigger Mitochondria-Mediated Apoptosis.},

author = {Tereza Kauerová and Tomáš Goněc and Josef Jampílek and Susanne Hafner and Ann-Kathrin Gaiser and Tatiana Syrovets and Radek Fedr and Karel Souček and Peter Kollar},

doi = {10.3390/ijms21103416},

issn = {1422-0067},

year  = {2020},

date = {2020-05-01},

journal = {International journal of molecular sciences},

volume = {21},

number = {10},

abstract = {Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were previously investigated for their antimycobacterial properties. In our study, we have shown their antiproliferative and cell death-inducing effects in cancer cell lines. Cell proliferation and viability were assessed by WST-1 assay and a dye exclusion test, respectively. Cell cycle distribution, phosphatidylserine externalization, levels of reactive oxygen or nitrogen species (RONS), mitochondrial membrane depolarization, and release of cytochrome c were estimated by flow cytometry. Levels of regulatory proteins were determined by Western blotting. Our data suggest that the ability to inhibit the proliferation of THP-1 or MCF-7 cells might be referred to meta- or para-substituted derivatives with electron-withdrawing groups -F, -Br, or -CF(3) at anilide moiety. This effect was accompanied by accumulation of cells in G1 phase. Compound 10 also induced apoptosis in THP-1 cells in association with a loss of mitochondrial membrane potential and production of mitochondrial superoxide. Our study provides a new insight into the action of salicylanilide derivatives, hydroxynaphthalene carboxamides, in cancer cells. Thus, their structure merits further investigation as a model moiety of new small-molecule compounds with potential anticancer properties.},

note = {Place: Switzerland},

keywords = {Anilides/chemistry/*pharmacology, Antineoplastic Agents/chemistry/pharmacology, antiproliferative effect, Apoptosis, Apoptosis/*drug effects, Cell Cycle, Cell Cycle/drug effects, Cell Proliferation/*drug effects, Cell Survival/drug effects, Humans, hydroxynaphthalene carboxamides, MCF-7 Cells, Membrane Potential, Mitochondria/*drug effects/metabolism, Mitochondrial/drug effects, Molecular Structure, Naphthols/*chemistry, Reactive Oxygen Species/metabolism, salicylanilides, Salicylanilides/chemistry/pharmacology, Structure-Activity Relationship, Superoxides/metabolism, THP-1 Cells},

pubstate = {published},

tppubtype = {article}

}

@article{tylichova_butyrate_2018,

title = {Butyrate and docosahexaenoic acid interact in alterations of specific lipid classes in differentiating colon cancer cells.},

author = {Zuzana Tylichová and Josef Slavík and Miroslav Ciganek and Petra Ovesná and Pavel Krčmář and Nicol Straková and Miroslav Machala and Alois Kozubík and Jiřina Hofmanová and Jan Vondráček},

doi = {10.1002/jcb.26641},

issn = {1097-4644 0730-2312},

year  = {2018},

date = {2018-06-01},

journal = {Journal of cellular biochemistry},

volume = {119},

number = {6},

pages = {4664–4679},

abstract = {Docosahexaenoic acid (DHA) and sodium butyrate (NaBt) exhibit a number of interactive effects on colon cancer cell growth, differentiation, or apoptosis; however, the molecular mechanisms responsible for these interactions and their impact on cellular lipidome are still not fully clear. Here, we show that both dietary agents together induce dynamic alterations of lipid metabolism, specific cellular lipid classes, and fatty acid composition. In HT-29 cell line, a model of differentiating colon carcinoma cells, NaBt supported incorporation of free DHA into non-polar lipids and their accumulation in cytoplasmic lipid droplets. DHA itself was not incorporated into sphingolipids; however, it significantly altered representation of individual ceramide (Cer) classes, in particular in combination with NaBt (DHA/NaBt). We observed altered expression of enzymes involved in Cer metabolism in cells treated with NaBt or DHA/NaBt, and exogenous Cer 16:0 was found to promote induction of apoptosis in differentiating HT-29 cells. NaBt, together with DHA, increased n-3 fatty acid synthesis and attenuated metabolism of monounsaturated fatty acids. Finally, DHA and/or NaBt altered expression of proteins involved in synthesis of fatty acids, including elongase 5, stearoyl CoA desaturase 1, or fatty acid synthase, with NaBt increasing expression of caveolin-1 and CD36 transporter, which may further promote DHA incorporation and its impact on cellular lipidome. In conclusion, our results indicate that interactions of DHA and NaBt exert complex changes in cellular lipidome, which may contribute to the alterations of colon cancer cell differentiation/apoptotic responses. The present data extend our knowledge about the nature of interactive effects of dietary fatty acids.},

note = {Place: United States},

keywords = {Apoptosis/*drug effects, Butyrate, Butyrates/*pharmacology, Cell Differentiation/*drug effects, Ceramides, Colon cancer, Colonic Neoplasms/*metabolism/pathology, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, Humans, lipid analyses, Lipid Metabolism/*drug effects, Membrane Lipids/classification/*metabolism, Phospholipids},

pubstate = {published},

tppubtype = {article}

}

@article{tylichova_activation_2017,

title = {Activation of autophagy and PPARγ protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation.},

author = {Zuzana Tylichová and Nicol Straková and Jan Vondráček and Alena Hyršlová Vaculová and Alois Kozubík and Jiřina Hofmanová},

doi = {10.1016/j.jnutbio.2016.09.006},

issn = {1873-4847 0955-2863},

year  = {2017},

date = {2017-01-01},

journal = {The Journal of nutritional biochemistry},

volume = {39},

pages = {145–155},

abstract = {The short-chain and n-3 polyunsaturated fatty acids exhibit anticancer properties, and they may mutually interact within the colon. However, the molecular mechanisms of their action in colon cancer cells are still not fully understood. Our study focused on the mechanisms responsible for the diverse effects of sodium butyrate (NaBt), in particular when interacting with docosahexaenoic acid (DHA), in distinct colon cancer cell types, in which NaBt either induces cell differentiation or activates programmed cell death involving mitochondrial pathway. NaBt activated autophagy both in HT-29 cells, which are sensitive to induction of differentiation, and in nondifferentiating HCT-116 cells. However, autophagy supported cell survival only in HT-29 cells. Combination of NaBt with DHA-promoted cell death, especially in HCT-116 cells and after longer time intervals. The inhibition of autophagy both attenuated differentiation and enhanced apoptosis in HT-29 cells treated with NaBt and DHA, but it had no effect in HCT-116 cells. NaBt, especially in combination with DHA, activated PPARγ in both cell types. PPARγ silencing decreased differentiation and increased apoptosis only in HT-29 cells, therefore we verified the role of caspases in apoptosis, differentiation and also PPARγ activity using a pan-caspase inhibitor. In summary, our data suggest that diverse responses of colon cancer cells to fatty acids may rely on their sensitivity to differentiation, which may in turn depend on distinct engagement of autophagy, caspases and PPARγ. These results contribute to understanding of mechanisms underlying differential effects of NaBt, when interacting with other dietary fatty acids, in colon cancer cells.},

note = {Place: United States},

keywords = {Antineoplastic Agents/pharmacology, Apoptosis/*drug effects, Autophagy, Autophagy/*drug effects, Butyrate, Butyrates/*pharmacology, Butyric Acid/pharmacology, Caspase 3/genetics/metabolism, Cell Differentiation/drug effects, Colon cancer, Colonic Neoplasms/*pathology, Differentiation, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, HT29 Cells, Humans, Mitochondria/drug effects/metabolism, PPAR gamma/genetics/*metabolism, PPARγ},

pubstate = {published},

tppubtype = {article}

}

@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{hruba_genotoxic_2010,

title = {Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells.},

author = {Eva Hrubá and Lenka Trilecová and Sona Marvanová and Pavel Krcmár and Lenka Vykopalová and Alena Milcová and Helena Líbalová and Jan Topinka and Andrea Starsíchová and Karel Soucek and Jan Vondrácek and Miroslav Machala},

doi = {10.1016/j.toxlet.2010.06.004},

issn = {1879-3169 0378-4274},

year  = {2010},

date = {2010-09-01},

journal = {Toxicology letters},

volume = {197},

number = {3},

pages = {227–235},

abstract = {Exposure to polycyclic aromatic hydrocarbons (PAHs) has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene (BaP), a potent mutagenic PAH, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. When analyzing the effect of BaP on the induction of CYP1 enzymes participating in the metabolic activation of PAHs in LNCaP cells, we found that BaP induced expression of CYP1A1 and CYP1A2, but not CYP1B1 enzyme. Despite a significant amount of DNA adducts being formed by BaP and, to a lesser extent also by another strong genotoxin, dibenzo[a,l]pyrene, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the phosphoinositide-3-kinase/Akt pro-survival pathway. The lack of apoptosis was not due a disruption of expression of pro-apoptotic and pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or checkpoint kinase-2. BaP did not activate p53, as evidenced by the lack of p53 accumulation, phosphorylation at Ser15, or induction of p53 transcriptional targets. Taken together, although genotoxic PAHs produced significant levels of DNA adducts in a model of human prostate carcinoma cells, they did not activate the mechanisms leading to elimination of cells with significant damage to DNA, presumably due to their failure to activate the p53-dependent DNA damage response.},

note = {Place: Netherlands},

keywords = {Animals, Apoptosis/*drug effects, Carcinoma/*metabolism, Cell Line, DNA Damage/*drug effects, Environmental Pollutants/toxicity, Gene Expression Regulation, Male, Neoplastic/drug effects, Polycyclic Aromatic Hydrocarbons/*toxicity, Prostatic Neoplasms/*metabolism, Tumor, Tumor Suppressor Protein p53/*metabolism},

pubstate = {published},

tppubtype = {article}

}

@article{ondrouskova_alternative_2008,

title = {Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis.},

author = {Eva Ondrousková and Karel Soucek and Viktor Horváth and Jan Smarda},

doi = {10.1016/j.leukres.2007.05.012},

issn = {0145-2126},

year  = {2008},

date = {2008-04-01},

journal = {Leukemia research},

volume = {32},

number = {4},

pages = {599–609},

abstract = {Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.},

note = {Place: England},

keywords = {Animals, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Arsenic Trioxide, Arsenicals/pharmacology, Autophagy/*drug effects, Blotting, Camptothecin/pharmacology, Caspases/*metabolism, Cell Line, Cell Transformation, Chickens, Cycloheximide/pharmacology, Fluorescence, Genes, Humans, Microscopy, myb/physiology, Necrosis, Neoplastic/*pathology, Oxides/pharmacology, Signal Transduction/*drug effects, Transformed, U937 Cells/drug effects, Western},

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{andrysik_activation_2006,

title = {Activation of ERK1/2 and p38 kinases by polycyclic aromatic hydrocarbons in rat liver epithelial cells is associated with induction of apoptosis.},

author = {Zdenek Andrysík and Miroslav Machala and Katerina Chramostová and Jirina Hofmanová and Alois Kozubík and Jan Vondrácek},

doi = {10.1016/j.taap.2005.06.007},

issn = {0041-008X},

year  = {2006},

date = {2006-03-01},

journal = {Toxicology and applied pharmacology},

volume = {211},

number = {3},

pages = {198–208},

abstract = {Deregulation of various signaling pathways, linked either to induction of cell proliferation or to modulation of cellular differentiation and apoptosis, has been proposed to contribute to carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). In the present study, we investigated effects of the PAHs previously shown to induce cell proliferation and/or apoptosis in contact-inhibited rat liver epithelial WB-F344 cells, with an aim to define the role of mitogen-activated protein kinases in both events. We found that only strong genotoxin dibenzo[a,l]pyrene (DBalP) activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase, but not c-Jun N-terminal kinases (JNKs), at concentrations inducing both apoptosis and phosphorylation of p53 tumor suppressor at serine 15 residue. In contrast, the PAHs stimulating cell proliferation in WB-F344 cell line had no effect on activation of ERK1/2, p38 or JNKs. Synthetic inhibitors of ERK1/2 activation (U0126) or p38 kinase activity (SB203580) prevented both apoptosis and induction of p53 phosphorylation by DBalP. Pifithrin-alpha, inhibitor of p53 transcriptional activity, prevented induction of apoptosis and activation of ERK1/2 and p38. Taken together, our data suggest that both ERK1/2 and p38 are activated in response to DBalP and that they might be involved in regulation of cellular response to DNA damage induced by DBalP, while neither kinase is involved in the release from contact inhibition induced by PAHs.},

note = {Place: United States},

keywords = {*Epithelial Cells/cytology/drug effects/enzymology, *Liver/cytology/drug effects/enzymology, Animals, Apoptosis/*drug effects, Cell Cycle/drug effects, Cell Line, Cell Proliferation/drug effects, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/*metabolism, JNK Mitogen-Activated Protein Kinases/metabolism, p38 Mitogen-Activated Protein Kinases/*metabolism, Phosphorylation, Polycyclic Aromatic Hydrocarbons/*toxicity, Rats},

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{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}

}