Ramushu Pearl, Mangoakoane Dikgale D, Makola Raymond T, Matsebatlela Thabe M
Department of Biochemistry, Microbiology and Biotechnology, Faculty of Science and Agriculture, University of Limpopo, P/bag x1106, Sovenga 0727, South Africa.
Molecules. 2025 Apr 17;30(8):1797. doi: 10.3390/molecules30081797.
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.
六十多年前，锂就已被确定为治疗躁郁症的首选药物。由于其价格低廉、稳定性好、副作用小以及具有免疫调节作用，近年来关于锂的研究主要集中在其潜在的抗癌特性和可能的作用机制上。肺癌是男性死亡的主要原因，死亡率高，生存率低。在本研究中，用不同浓度的氯化锂处理肺腺癌（A549）细胞，以评估其抗炎和抗癌特性。采用MTT [3-(4, 5-二甲基噻唑-2-基)-2, 5-二苯基四氮唑溴盐] 法、Muse细胞死亡检测法和细胞周期分析法评估氯化锂的体外细胞毒性作用。利用一氧化氮和氧化应激流式细胞术Muse检测法监测经锂处理的肺腺癌细胞的炎症特征。MTT活力检测表明，在浓度低于40 mM时，LiCl对非癌性RAW 264.7巨噬细胞的使用是安全的。锂以剂量依赖性方式降低细胞活力，诱导晚期凋亡细胞死亡，并破坏正常细胞周期进程，导致A549细胞在S期和G2/M期发生细胞周期阻滞。锂诱导A549细胞死亡伴随着活性氧和一氧化氮生成的增加。本研究表明，氯化锂对A549肺癌细胞具有一定的免疫调节细胞毒性作用，可进一步研究其在肺癌治疗中的应用。
