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{jendzelovsky_drug_2009,

title = {Drug efflux transporters, MRP1 and BCRP, affect the outcome of hypericin-mediated photodynamic therapy in HT-29 adenocarcinoma cells.},

author = {Rastislav Jendzelovský and Jaromír Mikes and Ján Koval' and Karel Soucek and Jirina Procházková and Martin Kello and Veronika Sacková and Jirina Hofmanová and Alois Kozubík and Peter Fedorocko},

doi = {10.1039/b9pp00086k},

issn = {1474-9092 1474-905X},

year  = {2009},

date = {2009-12-01},

journal = {Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology},

volume = {8},

number = {12},

pages = {1716–1723},

abstract = {Photodynamic therapy (PDT) is a flexible multi-target therapeutic approach. One of the main requirements of successful PDT is sufficient intracellular concentration of an applicable photosensitizer. Mechanisms of anticancer drug elimination by tumour cells are mostly linked to the elevated expression and activity of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP) and P450 monooxygenases. The interaction of hypericin with this cell drug-defence system is still unclear. We report here for the first time increased activity of MRP1 and BCRP in HT-29 colon cancer cells treated with hypericin per se. On the contrary, pre-treatment with proadifen (SKF525A) affected the function of MRP1 and BCRP leading to increased hypericin content, which might indicate a possible link between proadifen and these ABC transporter proteins. Subsequent enhanced intracellular oxidative stress was accompanied by loss of mitochondrial membrane potential, activation of caspase-9 and -3, PARP cleavage and onset of apoptosis. In conclusion, our study suggests that drug efflux transporters MRP1 and BCRP affect the pharmacokinetics of hypericin in HT-29 colon adenocarcinoma cells, and the action of hypericin-mediated PDT (HY-PDT) should be modulated by pre-treatment with their specific inhibitors.},

note = {Place: England},

keywords = {Adenocarcinoma/*drug therapy/secondary, Anthracenes, ATP Binding Cassette Transporter, ATP-Binding Cassette Transporters/*metabolism, Caspase 3/metabolism, Caspase 9/metabolism, Colonic Neoplasms/*drug therapy, Enzyme Inhibitors/pharmacology, HT29 Cells, Humans, Light, Member 1/metabolism, Member 2, Membrane Potential, Mitochondrial/drug effects, Mixed Function Oxygenases/metabolism, Multidrug Resistance-Associated Proteins/*metabolism, Neoplasm Proteins/*metabolism, Perylene/*analogs & derivatives/pharmacology, Photochemotherapy, Photosensitizing Agents/*pharmacology, Proadifen/pharmacology, Reactive Oxygen Species/metabolism, Subfamily B, Subfamily G},

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{harper_reappraisal_2005,

title = {A reappraisal of the genomic organization of human Nox1 and its splice variants.},

author = {Richart W. Harper and Changhong Xu and Karel Soucek and Henny Setiadi and Jason P. Eiserich},

doi = {10.1016/j.abb.2004.12.021},

issn = {0003-9861},

year  = {2005},

date = {2005-03-01},

journal = {Archives of biochemistry and biophysics},

volume = {435},

number = {2},

pages = {323–330},

abstract = {The recent discovery of non-phagocytic NAD(P)H oxidases belonging to the Nox family of enzymes sharing extensive homology to the leukocyte NAD(P)H oxidase has revolutionized our understanding of oxidative signaling related to fundamental biological processes and disease states. One form of this enzyme, Nox1, is a growth factor-responsive enzyme that catalyzes formation of the reactive oxygen species superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)). Its expression is linked to a number of biological responses including cellular proliferation, angiogenesis, and activation of cellular signaling pathways. Whereas early published studies have described three distinct isoforms of Nox1, the current body of literature fails to adequately recognize this notion. Also, functional differences between isoforms remain relatively unexplored. Herein, we report that expression of human Nox1 is restricted to two distinct isoforms derived from a single gene; that is, the full-length gene product and a shorter spliced variant which lacks one of the NAD(P)H binding domains. We have developed PCR primer sets that distinguish between the two forms of Nox1 in several human cell lines. We could not find evidence for expression of the shortest reported form of Nox1 (NOH-1S), previously identified as a proton channel, and the absence of paired splice sites in the gene suggests that it represents a reverse transcriptase artifact. A survey of the scientific literature reveals that the majority of studies related to Nox1 do not utilize molecular strategies that would adequately discern between the two Nox1 variants. The current literature suggest the two identified isoforms of human Nox1 (which we have named Nox1-L and Nox1-S) may be functionally distinct. Future studies related to Nox1 will benefit from establishing the identity of the Nox1 isoform expressed and the functions attributed to each variant.},

note = {Place: United States},

keywords = {*DNA Primers, *Genome, Alternative Splicing, Base Sequence, Caco-2 Cells, Computational Biology, Cultured, Epithelial Cells/enzymology, human, Humans, Hydrogen Peroxide/metabolism, Isoenzymes/genetics/metabolism, Male, Molecular Sequence Data, NADPH Oxidase 1, NADPH Oxidases/*genetics/metabolism, Prostate/enzymology, Reactive Oxygen Species/metabolism, Sequence Alignment, Superoxides/metabolism, Tumor 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}

}