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Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the ineffectiveness of the current therapies seriously limits the survival rate of NSCLC patients. In the search for new antitumor agents, nature has played a pivotal role providing a variety of molecules, which are likely...

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Autores principales: D’Abrosca, Brigida, Ciaramella, Vincenza, Graziani, Vittoria, Papaccio, Federica, Della Corte, Carminia Maria, Potenza, Nicoletta, Fiorentino, Antonio, Ciardiello, Fortunato, Morgillo, Floriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428841/
https://www.ncbi.nlm.nih.gov/pubmed/30899059
http://dx.doi.org/10.1038/s41598-019-41372-1
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author D’Abrosca, Brigida
Ciaramella, Vincenza
Graziani, Vittoria
Papaccio, Federica
Della Corte, Carminia Maria
Potenza, Nicoletta
Fiorentino, Antonio
Ciardiello, Fortunato
Morgillo, Floriana
author_facet D’Abrosca, Brigida
Ciaramella, Vincenza
Graziani, Vittoria
Papaccio, Federica
Della Corte, Carminia Maria
Potenza, Nicoletta
Fiorentino, Antonio
Ciardiello, Fortunato
Morgillo, Floriana
author_sort D’Abrosca, Brigida
collection PubMed
description Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the ineffectiveness of the current therapies seriously limits the survival rate of NSCLC patients. In the search for new antitumor agents, nature has played a pivotal role providing a variety of molecules, which are likely to exert selective anti-tumour properties. Herein, we investigated the antiproliferative potential of Urtica dioica L. extract (UD) against NSCLC cell models with low sensitivity to cisplatin, a cytotoxic agent largely employed to cure NSCLCs. UD inhibited cell proliferation in the selected cells, while no toxic effects were observed in normal lung cells. Furthermore, the co-treatment of UD and cisplatin notably sensitised NSCLC cells to cisplatin. Mechanistically, we discovered that UD-promoted endoplasmic reticulum (ER) stress via activation of the growth arrest and DNA damage-inducible gene 153 (GADD153) triggering apoptosis. We also performed an extensive NMR analysis of UD, identifying rutin and oxylipins as the main secondary metabolites present in the mixture. Additionally, we discovered that an oxylipins’ enriched fraction contributes to the antiproliferative activity of the plant extract. In the future, this study may provide new chemical scaffolds for the design of anti-cancer agents that target NSCLCs with low sensitivity to cisplatinum.
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spelling pubmed-64288412019-03-28 Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis D’Abrosca, Brigida Ciaramella, Vincenza Graziani, Vittoria Papaccio, Federica Della Corte, Carminia Maria Potenza, Nicoletta Fiorentino, Antonio Ciardiello, Fortunato Morgillo, Floriana Sci Rep Article Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the ineffectiveness of the current therapies seriously limits the survival rate of NSCLC patients. In the search for new antitumor agents, nature has played a pivotal role providing a variety of molecules, which are likely to exert selective anti-tumour properties. Herein, we investigated the antiproliferative potential of Urtica dioica L. extract (UD) against NSCLC cell models with low sensitivity to cisplatin, a cytotoxic agent largely employed to cure NSCLCs. UD inhibited cell proliferation in the selected cells, while no toxic effects were observed in normal lung cells. Furthermore, the co-treatment of UD and cisplatin notably sensitised NSCLC cells to cisplatin. Mechanistically, we discovered that UD-promoted endoplasmic reticulum (ER) stress via activation of the growth arrest and DNA damage-inducible gene 153 (GADD153) triggering apoptosis. We also performed an extensive NMR analysis of UD, identifying rutin and oxylipins as the main secondary metabolites present in the mixture. Additionally, we discovered that an oxylipins’ enriched fraction contributes to the antiproliferative activity of the plant extract. In the future, this study may provide new chemical scaffolds for the design of anti-cancer agents that target NSCLCs with low sensitivity to cisplatinum. Nature Publishing Group UK 2019-03-21 /pmc/articles/PMC6428841/ /pubmed/30899059 http://dx.doi.org/10.1038/s41598-019-41372-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
D’Abrosca, Brigida
Ciaramella, Vincenza
Graziani, Vittoria
Papaccio, Federica
Della Corte, Carminia Maria
Potenza, Nicoletta
Fiorentino, Antonio
Ciardiello, Fortunato
Morgillo, Floriana
Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title_full Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title_fullStr Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title_full_unstemmed Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title_short Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis
title_sort urtica dioica l. inhibits proliferation and enhances cisplatin cytotoxicity in nsclc cells via endoplasmic reticulum-stress mediated apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428841/
https://www.ncbi.nlm.nih.gov/pubmed/30899059
http://dx.doi.org/10.1038/s41598-019-41372-1
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