18β-Glycyrrhetinic Acid Has Anti-Cancer Effects via Inducing Apoptosis and G2/M Cell Cycle Arrest, and Inhibiting Migration of A549 Lung Cancer Cells

Background: 18 beta-glycyrrhetinic acid (18 beta-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established. Purpose: In this study, we investigated the underlying molecular mechanisms of 18 beta-Gly. Results: Our results showed that 18 beta-Gly had significant cytotoxic effects and no apparent side effects. 18 beta-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18 beta-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-kappa B) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced. Conclusion: In summary, 18 beta-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-kappa B signaling pathways in A549 lung cancer cells. Therefore, 18 beta-Gly is a novel promising candidate for the treatment of lung cancer.

Automated summary

The study demonstrated that 18 beta-glycyrrhetinic acid induces apoptosis and G2/M cell cycle arrest, as well as inhibits migration in A549 lung cancer cells through the activation of the ROS/MAPK/STAT3/NF-kappa B signaling pathways.