Journal Article

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

Chang, Gee-Chen, Chen, Min-Hsuan, Chang, Hsiu-Hui, Lin, Sheng-Yi, Lai, Yi-Hua, Lin, Ching-Hsiung, Tsai, Meng-Feng, Chen, Jeremy J. W.

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Agricultural biotechnology / Anticancer properties / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Assaying / Autophagy / Cancer / Cancer prevention / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - enzymology / Carcinoma, Non-Small-Cell Lung - pathology / Cell Death - drug effects / Cell Line, Tumor / Cell Movement - drug effects / Cell proliferation / Cell Survival - drug effects / Chemotherapy / Colonies / Cytotoxicity / Development and progression / Digoxin / Digoxin - pharmacology / Digoxin - therapeutic use / Enzyme Activation - drug effects / Epidermal growth factor / Epidermal growth factor receptors / Focal Adhesion Protein-Tyrosine Kinases - metabolism / Gastric cancer / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Health aspects / Humans / Hypoxia / Internal medicine / Kinases / Lung cancer / Lung diseases / Lung Neoplasms - drug therapy / Lung Neoplasms - enzymology / Lung Neoplasms - pathology / Malignancy / Medical prognosis / Medicine / Metastasis / Models, Biological / mRNA / Mutation / Neoplasm Invasiveness / Non-small cell lung cancer / Non-small cell lung carcinoma / Phosphorylation - drug effects / Proteins / Receptor, Epidermal Growth Factor - genetics / Receptor, Epidermal Growth Factor - metabolism / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents / Signal Transduction - drug effects / Signaling / Small cell lung cancer / Src protein / src-Family Kinases - metabolism / Stat3 protein / STAT3 Transcription Factor - metabolism / Stomach cancer / Toxicity / Tumor cell lines / Tumor Stem Cell Assay / Tumors / Western blotting