Abstract
Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumor effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the two cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial–mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signaling molecules of the PI3K/Akt pathway that are known to be involved in tumor cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required.
Highlights
Lung cancer is the most commonly diagnosed cancer in the world, with approximately 1,762,450 cancer cases diagnosed in 2019 [1]
Digoxin reduced the viability of nonsmall cell lung cancer cells in vitro To investigate the toxic effect of digoxin on nonsmall cell lung cancer cells, we assessed the cellular viabilities of A549 and H1299 cells treated with digoxin at various concentrations by an MTT assay and a plate colony formation assay
We found that digoxin exerted antitumor activities on Nonsmall cell lung cancer (NSCLC) A549 and H1299 cells by inhibiting cancer cell proliferation and inducing cell arrest and autophagy
Summary
Lung cancer is the most commonly diagnosed cancer in the world, with approximately 1,762,450 cancer cases diagnosed in 2019 [1]. Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers and has the highest cancer mortality rate [2]. Metastasis is a major cause of morbidity and mortality in NSCLC. Lung carcinomas at the time of diagnosis are most often in the metastatic stage [3,4]. Lung cancer can metastasize to different sites, such as the brain, bone and adrenal glands [5,6]. Current treatments for NSCLC, including surgery, chemotherapy, radiation and targeted therapies, are far from meeting clinical requirements [7]. It is urgent to find more efficient potential antitumor drugs for lung cancer therapy
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