2020
Kauerová, Tereza; Goněc, Tomáš; Jampílek, Josef; Hafner, Susanne; Gaiser, Ann-Kathrin; Syrovets, Tatiana; Fedr, Radek; Souček, Karel; Kollar, Peter
Ring-Substituted 1-Hydroxynaphthalene-2-Carboxanilides Inhibit Proliferation and Trigger Mitochondria-Mediated Apoptosis. Journal Article
In: International journal of molecular sciences, vol. 21, no. 10, 2020, ISSN: 1422-0067, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: 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
@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}
}
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.
2005
Harper, Richart W.; Xu, Changhong; Soucek, Karel; Setiadi, Henny; Eiserich, Jason P.
A reappraisal of the genomic organization of human Nox1 and its splice variants. Journal Article
In: Archives of biochemistry and biophysics, vol. 435, no. 2, pp. 323–330, 2005, ISSN: 0003-9861, (Place: United States).
Abstract | Links | BibTeX | Tags: *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
@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}
}
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.