Formoterol exerts anti-cancer effects modulating oxidative stress and EMT processes in CSE exposed lung adenocarcinoma cells

Abstract

<b>Background:</b> Lung cancer, the leading cause of morbidity and mortality worldwide, frequently affects patients with history of Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke exposure is considered the main risk factor for COPD and lung cancer.&nbsp;Cigarette smoke, increasing oxidative stress and modulating epithelial–mesenchymal transition (EMT) processes in cancer cells, favours cancer progression. Formoterol (FO), a long-acting β2-agonist widely used for COPD treatment, exerts anti-oxidant activities. <b>Aim:</b> this study explored in lung adenocarcinoma cell line (A549) whether FO was able to counteract the effects of cigarette smoke extract (CSE) exposure on oxidative stress and EMT processes. <b>Methods:</b> A549 were stimulated with CSE and FO alone or combined, ROS and mitochondrial superoxide were evaluated by flow-cytometry and EMT markers (E-cadherin, SNAIL1) were evaluated by flow-cytometry and Real-Time PCR. <b>Results:</b> CSE increased production of ROS and mitochondrial superoxide, decreased E-cadherin and increased SNAIL1. FO reverted all these phenomena in CSE stimulated A549 cells. <b>Conclusions:</b> the present study provides intriguing evidence that FO might exert anti-cancer effects reverting oxidative stress and some EMT processes due to cigarette smoke exposure in lung adenocarcinoma cells. These evidences must be validated in future clinical studies to support a repositioning of FO as add on treatment for lung cancer management.