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ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells
This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited the most potent activity with IC(50) = 8.0 μM in human col...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271261/ https://www.ncbi.nlm.nih.gov/pubmed/25068784 http://dx.doi.org/10.3390/molecules190810877 |
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author | Kello, Martin Drutovic, David Chripkova, Martina Pilatova, Martina Budovska, Mariana Kulikova, Lucia Urdzik, Peter Mojzis, Jan |
author_facet | Kello, Martin Drutovic, David Chripkova, Martina Pilatova, Martina Budovska, Mariana Kulikova, Lucia Urdzik, Peter Mojzis, Jan |
author_sort | Kello, Martin |
collection | PubMed |
description | This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited the most potent activity with IC(50) = 8.0 μM in human colorectal Caco2 cells and was selected for further studies. The flow cytometric analysis revealed a K1-induced increase in the G(2)/M phase associated with dysregulation of α-tubulin, α(1)-tubulin and β(5)-tubulin expression. These findings suggest that the inhibitory effect of K1 can be mediated via inhibition of microtubule formation. Furthermore, simultaneously with G(2)/M arrest, K1 also increased population of cells with sub-G(1) DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V/PI double staining, DNA fragmentation assay and chromatin condensation assay. The apoptosis was associated with the loss of mitochondrial membrane potential (MMP), caspase-3 activation as well as intracellular reactive oxygen species (ROS) production. Moreover, the antioxidant Trolox blocked ROS production, changes in MMP and decreased K1 cytotoxicity, which confirmed the important role of ROS in cell apoptosis. Taken together, our data demonstrate that K1 induces ROS-dependent apoptosis in Caco2 cells and provide the rationale for further in vivo anticancer investigation. |
format | Online Article Text |
id | pubmed-6271261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62712612018-12-27 ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells Kello, Martin Drutovic, David Chripkova, Martina Pilatova, Martina Budovska, Mariana Kulikova, Lucia Urdzik, Peter Mojzis, Jan Molecules Article This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited the most potent activity with IC(50) = 8.0 μM in human colorectal Caco2 cells and was selected for further studies. The flow cytometric analysis revealed a K1-induced increase in the G(2)/M phase associated with dysregulation of α-tubulin, α(1)-tubulin and β(5)-tubulin expression. These findings suggest that the inhibitory effect of K1 can be mediated via inhibition of microtubule formation. Furthermore, simultaneously with G(2)/M arrest, K1 also increased population of cells with sub-G(1) DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V/PI double staining, DNA fragmentation assay and chromatin condensation assay. The apoptosis was associated with the loss of mitochondrial membrane potential (MMP), caspase-3 activation as well as intracellular reactive oxygen species (ROS) production. Moreover, the antioxidant Trolox blocked ROS production, changes in MMP and decreased K1 cytotoxicity, which confirmed the important role of ROS in cell apoptosis. Taken together, our data demonstrate that K1 induces ROS-dependent apoptosis in Caco2 cells and provide the rationale for further in vivo anticancer investigation. MDPI 2014-07-25 /pmc/articles/PMC6271261/ /pubmed/25068784 http://dx.doi.org/10.3390/molecules190810877 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Kello, Martin Drutovic, David Chripkova, Martina Pilatova, Martina Budovska, Mariana Kulikova, Lucia Urdzik, Peter Mojzis, Jan ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title | ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title_full | ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title_fullStr | ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title_full_unstemmed | ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title_short | ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells |
title_sort | ros-dependent antiproliferative effect of brassinin derivative homobrassinin in human colorectal cancer caco2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271261/ https://www.ncbi.nlm.nih.gov/pubmed/25068784 http://dx.doi.org/10.3390/molecules190810877 |
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