Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress
Abstract: Larrea divaricata is a plant with antiproliferative principles. We have previously identified the flavonoid quercetin-3-methyl ether (Q-3-ME) in an ethyl acetate fraction (EA). Both the extract and Q-3-ME were found to be effective against the EL-4 T lymphoma cell line. However, the mechanism underlying the inhibition of tumor cell proliferation remains to be elucidated. In this work, we analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by Q-3-ME and EA. Both treatments were able to induce apoptosis in a concentration-dependent and time-dependent manner. The western blot analysis revealed a sequential activation of caspases-9 and 3, followed by poly-(ADP-ribose)-polymerase cleavage. EA and Q-3-ME lowered the mitochondrial membrane potential, showing the activation of the intrinsic pathway of apoptosis. Q-3-ME and EA increased NO production and inducible NO synthase expression in tumor cells. The involvement of NO in cell death was confirmed by the nitric oxide synthases inhibitor L-NAME. In addition, EA and Q-3-ME induced a cell cycle arrest in G0/G1 phase. These drugs did not affect normal cell viability. This data suggested that EA and Q-3-ME induce an increase in NO production that would lead to the cell cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright © 2016 John Wiley & Sons, Ltd.
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2016
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Subjects: | APOPTOSIS, LARREA DIVARICATA, LINFOMA DE CELULAS T, ETIL ACETATO, OXIDO NITRICO, POLIFENOLES, QUERCETINA, LINFOMAS, |
Online Access: | https://repositorio.uca.edu.ar/handle/123456789/15337 |
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oai:ucacris:123456789-153372022-10-28T05:01:09Z Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress Martino, Renzo Barreiro Arcos, María Laura Alonso, Rosario Sülsen, Valeria Cremaschi, Graciela A. Anesini, Claudia APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS Abstract: Larrea divaricata is a plant with antiproliferative principles. We have previously identified the flavonoid quercetin-3-methyl ether (Q-3-ME) in an ethyl acetate fraction (EA). Both the extract and Q-3-ME were found to be effective against the EL-4 T lymphoma cell line. However, the mechanism underlying the inhibition of tumor cell proliferation remains to be elucidated. In this work, we analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by Q-3-ME and EA. Both treatments were able to induce apoptosis in a concentration-dependent and time-dependent manner. The western blot analysis revealed a sequential activation of caspases-9 and 3, followed by poly-(ADP-ribose)-polymerase cleavage. EA and Q-3-ME lowered the mitochondrial membrane potential, showing the activation of the intrinsic pathway of apoptosis. Q-3-ME and EA increased NO production and inducible NO synthase expression in tumor cells. The involvement of NO in cell death was confirmed by the nitric oxide synthases inhibitor L-NAME. In addition, EA and Q-3-ME induced a cell cycle arrest in G0/G1 phase. These drugs did not affect normal cell viability. This data suggested that EA and Q-3-ME induce an increase in NO production that would lead to the cell cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright © 2016 John Wiley & Sons, Ltd. 2022-10-27T11:35:51Z 2022-10-27T11:35:51Z 2016 Artículo Martino, R., et al. Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress [en línea]. Phytotherapy Research. 2016, 30(7) doi:10.1002/ptr.5615 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/15337 0951-418X 1099-1573 (online) https://repositorio.uca.edu.ar/handle/123456789/15337 10.1002/ptr.5615 27038396 eng Acceso Restringido http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Phytotherapy Research. 2016, 30(7) |
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APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS |
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APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS Martino, Renzo Barreiro Arcos, María Laura Alonso, Rosario Sülsen, Valeria Cremaschi, Graciela A. Anesini, Claudia Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
description |
Abstract: Larrea divaricata is a plant with antiproliferative principles. We have previously identified the flavonoid quercetin-3-methyl ether (Q-3-ME) in an ethyl acetate fraction (EA). Both the extract and Q-3-ME were found to be effective against the EL-4 T lymphoma cell line. However, the mechanism underlying the inhibition of tumor cell proliferation remains to be elucidated. In this work, we analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by Q-3-ME and EA. Both treatments were able to induce apoptosis in a concentration-dependent and time-dependent manner. The western blot analysis revealed a sequential activation of caspases-9 and 3, followed by poly-(ADP-ribose)-polymerase cleavage. EA and Q-3-ME lowered the mitochondrial membrane potential, showing the activation of the intrinsic pathway of apoptosis. Q-3-ME and EA increased NO production and inducible NO synthase expression in tumor cells. The involvement of NO in cell death was confirmed by the nitric oxide synthases inhibitor L-NAME. In addition, EA and Q-3-ME induced a cell cycle arrest in G0/G1 phase. These drugs did not affect normal cell viability. This data suggested that EA and Q-3-ME induce an increase in NO production that would lead to the cell cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright © 2016 John Wiley & Sons, Ltd. |
format |
Artículo |
topic_facet |
APOPTOSIS LARREA DIVARICATA LINFOMA DE CELULAS T ETIL ACETATO OXIDO NITRICO POLIFENOLES QUERCETINA LINFOMAS |
author |
Martino, Renzo Barreiro Arcos, María Laura Alonso, Rosario Sülsen, Valeria Cremaschi, Graciela A. Anesini, Claudia |
author_facet |
Martino, Renzo Barreiro Arcos, María Laura Alonso, Rosario Sülsen, Valeria Cremaschi, Graciela A. Anesini, Claudia |
author_sort |
Martino, Renzo |
title |
Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
title_short |
Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
title_full |
Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
title_fullStr |
Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
title_full_unstemmed |
Polyphenol-rich fraction from Larrea divaricata and its main flavonoid Quercetin-3-Methyl Ether induce apoptosis in lymphoma cells through nitrosative stress |
title_sort |
polyphenol-rich fraction from larrea divaricata and its main flavonoid quercetin-3-methyl ether induce apoptosis in lymphoma cells through nitrosative stress |
publisher |
Wiley |
publishDate |
2016 |
url |
https://repositorio.uca.edu.ar/handle/123456789/15337 |
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