title: Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer.
abstract: 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.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Sheng-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hsiu-Hui
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Lai
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ching-Hsiung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Min-Hsuan
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.affiliation: Department of Molecular Biotechnology, Dayeh University, Changhua, Taiwan.
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D004077:Digoxin; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases