Propafenone suppresses esophageal cancer proliferation through inducing mitochondrial dysfunction.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival and limited therapeutic options. The aim of this study is to identify novel anticancer strategies from existing Food and Drug Administration (FDA)-approved drugs that have been used to clinically treat other diseases. Here, propafenone, an antiarrhythmic medication, was found to induce apoptosis and exert a significantly inhibitory effect on the proliferation and colony-forming ability of ESCC cells in a dose-dependent manner without observed cytotoxicity on normal esophageal epithelial cells. Furthermore, propafenone markedly suppressed growth of tumor xenografts in nude mice by reducing the Ki-67 proliferation index and angiogenesis but did not damage the vital organs of the animals. Mechanistically, our data from the proteomics, Western blot and flow cytometry analyses demonstrated that propafenone caused mitochondrial dysfunction as indicated by a decreased mitochondrial membrane potential and reduced expression of Bcl-xL and Bcl-2. In summary, this study provides the first evidence that propafenone, an FDA-approved drug to treat arrhythmias, could be a novel therapeutic strategy for treating ESCC without obvious side effects.