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Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1

Tetracenomycin X (Tcm X) has been reported to have antitumour activity in various cancers, but there have not been any studies on its activity with respect to lung cancer to date. Therefore, this study aims to investigate the anti-lung cancer activity of Tcm X. In this study, we found that tetraceno...

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Autores principales: Qiao, Xinran, Gan, Maoluo, Wang, Chen, Liu, Bin, Shang, Yue, Li, Yi, Chen, Shuzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357012/
https://www.ncbi.nlm.nih.gov/pubmed/30669360
http://dx.doi.org/10.3390/md17010063
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author Qiao, Xinran
Gan, Maoluo
Wang, Chen
Liu, Bin
Shang, Yue
Li, Yi
Chen, Shuzhen
author_facet Qiao, Xinran
Gan, Maoluo
Wang, Chen
Liu, Bin
Shang, Yue
Li, Yi
Chen, Shuzhen
author_sort Qiao, Xinran
collection PubMed
description Tetracenomycin X (Tcm X) has been reported to have antitumour activity in various cancers, but there have not been any studies on its activity with respect to lung cancer to date. Therefore, this study aims to investigate the anti-lung cancer activity of Tcm X. In this study, we found that tetracenomycin X showed antitumour activity in vivo and selectively inhibited the proliferation of lung cancer cells without influencing lung fibroblasts. In addition, apoptosis and autophagy did not contribute to the antitumour activity. Tetracenomycin X exerts antitumour activity through cell cycle arrest induced by the downregulation of cyclin D1. To explore the specific mechanism, we found that tetracenomycin X directly induced cyclin D1 proteasomal degradation and indirectly downregulated cyclin D1 via the activation of p38 and c-JUN proteins. All these findings were explored for the first time, which indicated that tetracenomycin X may be a powerful antimitotic class of anticancer drug candidates for the treatment of lung cancer in the future.
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spelling pubmed-63570122019-02-05 Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1 Qiao, Xinran Gan, Maoluo Wang, Chen Liu, Bin Shang, Yue Li, Yi Chen, Shuzhen Mar Drugs Article Tetracenomycin X (Tcm X) has been reported to have antitumour activity in various cancers, but there have not been any studies on its activity with respect to lung cancer to date. Therefore, this study aims to investigate the anti-lung cancer activity of Tcm X. In this study, we found that tetracenomycin X showed antitumour activity in vivo and selectively inhibited the proliferation of lung cancer cells without influencing lung fibroblasts. In addition, apoptosis and autophagy did not contribute to the antitumour activity. Tetracenomycin X exerts antitumour activity through cell cycle arrest induced by the downregulation of cyclin D1. To explore the specific mechanism, we found that tetracenomycin X directly induced cyclin D1 proteasomal degradation and indirectly downregulated cyclin D1 via the activation of p38 and c-JUN proteins. All these findings were explored for the first time, which indicated that tetracenomycin X may be a powerful antimitotic class of anticancer drug candidates for the treatment of lung cancer in the future. MDPI 2019-01-18 /pmc/articles/PMC6357012/ /pubmed/30669360 http://dx.doi.org/10.3390/md17010063 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
Qiao, Xinran
Gan, Maoluo
Wang, Chen
Liu, Bin
Shang, Yue
Li, Yi
Chen, Shuzhen
Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title_full Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title_fullStr Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title_full_unstemmed Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title_short Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1
title_sort tetracenomycin x exerts antitumour activity in lung cancer cells through the downregulation of cyclin d1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357012/
https://www.ncbi.nlm.nih.gov/pubmed/30669360
http://dx.doi.org/10.3390/md17010063
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