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The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isol...

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Autores principales: Martínez-García, David, Pérez-Hernández, Marta, Korrodi-Gregório, Luís, Quesada, Roberto, Ramos, Ricard, Baixeras, Núria, Pérez-Tomás, Ricardo, Soto-Cerrato, Vanessa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724027/
https://www.ncbi.nlm.nih.gov/pubmed/31412593
http://dx.doi.org/10.3390/biom9080361
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author Martínez-García, David
Pérez-Hernández, Marta
Korrodi-Gregório, Luís
Quesada, Roberto
Ramos, Ricard
Baixeras, Núria
Pérez-Tomás, Ricardo
Soto-Cerrato, Vanessa
author_facet Martínez-García, David
Pérez-Hernández, Marta
Korrodi-Gregório, Luís
Quesada, Roberto
Ramos, Ricard
Baixeras, Núria
Pérez-Tomás, Ricardo
Soto-Cerrato, Vanessa
author_sort Martínez-García, David
collection PubMed
description Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment.
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spelling pubmed-67240272019-09-10 The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models Martínez-García, David Pérez-Hernández, Marta Korrodi-Gregório, Luís Quesada, Roberto Ramos, Ricard Baixeras, Núria Pérez-Tomás, Ricardo Soto-Cerrato, Vanessa Biomolecules Article Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment. MDPI 2019-08-13 /pmc/articles/PMC6724027/ /pubmed/31412593 http://dx.doi.org/10.3390/biom9080361 Text en © 2019 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martínez-García, David
Pérez-Hernández, Marta
Korrodi-Gregório, Luís
Quesada, Roberto
Ramos, Ricard
Baixeras, Núria
Pérez-Tomás, Ricardo
Soto-Cerrato, Vanessa
The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title_full The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title_fullStr The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title_full_unstemmed The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title_short The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
title_sort natural-based antitumor compound t21 decreases survivin levels through potent stat3 inhibition in lung cancer models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724027/
https://www.ncbi.nlm.nih.gov/pubmed/31412593
http://dx.doi.org/10.3390/biom9080361
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