Lithium Induces Oxidative Stress, Apoptotic Cell Death, and G2/M Phase Cell Cycle Arrest in A549 Lung Cancer Cells

Lithium has been identified more than six decades ago as a preferred treatment option for manic depression. Due to its affordability, stability, minimal side effects, and immunomodulatory effects, recent studies on lithium have focused on its potential anticancer properties and possible mechanisms of action. Lung cancer ranks the highest as the main cause of death in males and has high mortality rates with low survival rates. In this study, lung adenocarcinoma (A549) cells were treated with various concentrations of lithium chloride to evaluate its inflammatory and anticancer properties. The in vitro cytotoxic effects of lithium chloride were assessed using the MTT [3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, Muse® cell death, and cell cycle analysis. The nitric oxide and oxidative stress flow cytometry Muse® assays were used to monitor inflammation profiles of lithium-treated lung adenocarcinoma cells. The MTT viability assay showed the safe use of LiCl on the noncancerous RAW 264.7 macrophage cells below a concentration of 40 mM. Lithium reduced cell viability, induced late apoptotic cell death, and disrupted normal cell cycle progression in a dose-dependent manner, leading to cell cycle arrest in the S and G2/M phases of A549 cells. The induction of cell death by lithium in A549 cells is accompanied by increased ROS and nitric oxide production. This study shows that lithium chloride possesses some immunomodulatory cytotoxic effects on A549 lung cancer cells and can be further investigated for use in lung cancer treatment.