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DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models
Lung cancer is one of the deadliest cancers worldwide due to chemoresistance in patients with late-stage disease. Quinoline derivatives show biological activity against HIV, malaria, bacteriuria, and cancer. DFIQ is a novel synthetic quinoline derivative that induces cell death in both in vitro and...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281296/ https://www.ncbi.nlm.nih.gov/pubmed/32466291 http://dx.doi.org/10.3390/cancers12051348 |
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author | Huang, Hurng-Wern Bow, Yung-Ding Wang, Chia-Yih Chen, Yen-Chun Fu, Pei-Rong Chang, Kuo-Feng Wang, Tso-Wen Tseng, Chih-Hua Chen, Yeh-Long Chiu, Chien-Chih |
author_facet | Huang, Hurng-Wern Bow, Yung-Ding Wang, Chia-Yih Chen, Yen-Chun Fu, Pei-Rong Chang, Kuo-Feng Wang, Tso-Wen Tseng, Chih-Hua Chen, Yeh-Long Chiu, Chien-Chih |
author_sort | Huang, Hurng-Wern |
collection | PubMed |
description | Lung cancer is one of the deadliest cancers worldwide due to chemoresistance in patients with late-stage disease. Quinoline derivatives show biological activity against HIV, malaria, bacteriuria, and cancer. DFIQ is a novel synthetic quinoline derivative that induces cell death in both in vitro and in vivo zebrafish xenograft models. DFIQ induced cell death, including apoptosis, and the IC(50) values were 4.16 and 2.31 μM at 24 and 48 h, respectively. DFIQ was also found to induce apoptotic protein cleavage and DNA damage, reduce cell cycle-associated protein expression, and disrupt reactive oxygen species (ROS) reduction, thus resulting in the accumulation of superoxide radicals. Autophagy is also a necessary process associated with chemotherapy-induced cell death. Lysosome accumulation and lysosome-associated membrane protein-2 (LAMP2) depletion were observed after DFIQ treatment, and cell death induction was restored upon treatment with the autophagy inhibitor 3-methyladenine (3-MA). Nevertheless, ROS production was found to be involved in DFIQ-induced autophagy activation and LAMP2 depletion. Our data provide the first evidence for developing DFIQ for clinical usage and show the regulatory mechanism by which DFIQ affects ROS, autophagy, and apoptosis. |
format | Online Article Text |
id | pubmed-7281296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72812962020-06-19 DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models Huang, Hurng-Wern Bow, Yung-Ding Wang, Chia-Yih Chen, Yen-Chun Fu, Pei-Rong Chang, Kuo-Feng Wang, Tso-Wen Tseng, Chih-Hua Chen, Yeh-Long Chiu, Chien-Chih Cancers (Basel) Article Lung cancer is one of the deadliest cancers worldwide due to chemoresistance in patients with late-stage disease. Quinoline derivatives show biological activity against HIV, malaria, bacteriuria, and cancer. DFIQ is a novel synthetic quinoline derivative that induces cell death in both in vitro and in vivo zebrafish xenograft models. DFIQ induced cell death, including apoptosis, and the IC(50) values were 4.16 and 2.31 μM at 24 and 48 h, respectively. DFIQ was also found to induce apoptotic protein cleavage and DNA damage, reduce cell cycle-associated protein expression, and disrupt reactive oxygen species (ROS) reduction, thus resulting in the accumulation of superoxide radicals. Autophagy is also a necessary process associated with chemotherapy-induced cell death. Lysosome accumulation and lysosome-associated membrane protein-2 (LAMP2) depletion were observed after DFIQ treatment, and cell death induction was restored upon treatment with the autophagy inhibitor 3-methyladenine (3-MA). Nevertheless, ROS production was found to be involved in DFIQ-induced autophagy activation and LAMP2 depletion. Our data provide the first evidence for developing DFIQ for clinical usage and show the regulatory mechanism by which DFIQ affects ROS, autophagy, and apoptosis. MDPI 2020-05-25 /pmc/articles/PMC7281296/ /pubmed/32466291 http://dx.doi.org/10.3390/cancers12051348 Text en © 2020 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 Huang, Hurng-Wern Bow, Yung-Ding Wang, Chia-Yih Chen, Yen-Chun Fu, Pei-Rong Chang, Kuo-Feng Wang, Tso-Wen Tseng, Chih-Hua Chen, Yeh-Long Chiu, Chien-Chih DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title | DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title_full | DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title_fullStr | DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title_full_unstemmed | DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title_short | DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models |
title_sort | dfiq, a novel quinoline derivative, shows anticancer potential by inducing apoptosis and autophagy in nsclc cell and in vivo zebrafish xenograft models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281296/ https://www.ncbi.nlm.nih.gov/pubmed/32466291 http://dx.doi.org/10.3390/cancers12051348 |
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