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 6 decades ago as a preferred treatment option for manic depression. As a result of its affordability, stability, minimal side effects, and immunomodulatory effects, recent lithium studies have focused on its anti-cancer potential and possible mechanism 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 anti-inflammatory and anti-cancer effects. 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 safe use of LiCl on the noncancerous Raw 264.7 macrophage cells below the concentration of 40 mM. Lithium reduced cell viability, induces late apoptotic cell death, and disrupts 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 accompanied increased ROS and nitric oxide production. This study shows that lithium chloride possess some immunomodulatory cytotoxic effects on A549 lung cancer cells and can be further investigated for use in lung cancer treatment.