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Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer

Non-small cell lung cancer is the predominant type of lung cancer, resulting in high mortality worldwide. Digoxin, a cardiac glycoside, has recently been suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an important role in cancer progression and is therefore a potential...

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Autores principales: Lin, Sheng-Yi, Chang, Hsiu-Hui, Lai, Yi-Hua, Lin, Ching-Hsiung, Chen, Min-Hsuan, Chang, Gee-Chen, Tsai, Meng-Feng, Chen, Jeremy J. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425490/
https://www.ncbi.nlm.nih.gov/pubmed/25955608
http://dx.doi.org/10.1371/journal.pone.0123305
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author Lin, Sheng-Yi
Chang, Hsiu-Hui
Lai, Yi-Hua
Lin, Ching-Hsiung
Chen, Min-Hsuan
Chang, Gee-Chen
Tsai, Meng-Feng
Chen, Jeremy J. W.
author_facet Lin, Sheng-Yi
Chang, Hsiu-Hui
Lai, Yi-Hua
Lin, Ching-Hsiung
Chen, Min-Hsuan
Chang, Gee-Chen
Tsai, Meng-Feng
Chen, Jeremy J. W.
author_sort Lin, Sheng-Yi
collection PubMed
description Non-small cell lung cancer is the predominant type of lung cancer, resulting in high mortality worldwide. Digoxin, a cardiac glycoside, has recently been suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an important role in cancer progression and is therefore a potential target for cancer therapy. Here, we investigated whether digoxin could suppress lung cancer progression through the inhibition of Src activity. The effects of digoxin on lung cancer cell functions were investigated using colony formation, migration and invasion assays. Western blotting and qPCR assays were used to analyze the mRNA and protein expression levels of Src and its downstream proteins, and a cell viability assay was used to measure cellular cytotoxicity effects. The results of the cell function assays revealed that digoxin inhibited the proliferation, invasion, migration, and colony formation of A549 lung cancer cells. Similar effects of digoxin were also observed in other lung cancer cell lines. Furthermore, we found that digoxin significantly suppressed Src activity and its protein expression in a dose- and time-dependent manner as well as reduced EGFR and STAT3 activity. Our data suggest that digoxin is a potential anticancer agent that may suppress lung cancer progression through inhibiting Src and the activity of related proteins.
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spelling pubmed-44254902015-05-21 Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer Lin, Sheng-Yi Chang, Hsiu-Hui Lai, Yi-Hua Lin, Ching-Hsiung Chen, Min-Hsuan Chang, Gee-Chen Tsai, Meng-Feng Chen, Jeremy J. W. PLoS One Research Article Non-small cell lung cancer is the predominant type of lung cancer, resulting in high mortality worldwide. Digoxin, a cardiac glycoside, has recently been suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an important role in cancer progression and is therefore a potential target for cancer therapy. Here, we investigated whether digoxin could suppress lung cancer progression through the inhibition of Src activity. The effects of digoxin on lung cancer cell functions were investigated using colony formation, migration and invasion assays. Western blotting and qPCR assays were used to analyze the mRNA and protein expression levels of Src and its downstream proteins, and a cell viability assay was used to measure cellular cytotoxicity effects. The results of the cell function assays revealed that digoxin inhibited the proliferation, invasion, migration, and colony formation of A549 lung cancer cells. Similar effects of digoxin were also observed in other lung cancer cell lines. Furthermore, we found that digoxin significantly suppressed Src activity and its protein expression in a dose- and time-dependent manner as well as reduced EGFR and STAT3 activity. Our data suggest that digoxin is a potential anticancer agent that may suppress lung cancer progression through inhibiting Src and the activity of related proteins. Public Library of Science 2015-05-08 /pmc/articles/PMC4425490/ /pubmed/25955608 http://dx.doi.org/10.1371/journal.pone.0123305 Text en © 2015 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lin, Sheng-Yi
Chang, Hsiu-Hui
Lai, Yi-Hua
Lin, Ching-Hsiung
Chen, Min-Hsuan
Chang, Gee-Chen
Tsai, Meng-Feng
Chen, Jeremy J. W.
Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title_full Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title_fullStr Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title_full_unstemmed Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title_short Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer
title_sort digoxin suppresses tumor malignancy through inhibiting multiple src-related signaling pathways in non-small cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425490/
https://www.ncbi.nlm.nih.gov/pubmed/25955608
http://dx.doi.org/10.1371/journal.pone.0123305
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