OncoTargets and Therapy (Oct 2021)

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

  • Luo YH,
  • Wang C,
  • Xu WT,
  • Zhang Y,
  • Zhang T,
  • Xue H,
  • Li YN,
  • Fu ZR,
  • Wang Y,
  • Jin CH

Journal volume & issue
Vol. Volume 14
pp. 5131 – 5144

Abstract

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Ying-Hua Luo,1,* Cheng Wang,2,* Wan-Ting Xu,3,* Yu Zhang,3 Tong Zhang,3 Hui Xue,3 Yan-Nan Li,3 Zhong-Ren Fu,3 Ying Wang,4 Cheng-Hao Jin3– 5 1Department of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 2Pharmacy Department, Daqing Oilfield General Hospital, Daqing, 163001, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 4College of Food Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 5National Coarse Cereals Engineering Research Center, Daqing, 163319, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng-Hao Jin; Ying Wang Email [email protected]; [email protected]: 18β-glycyrrhetinic acid (18β-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 18β-Gly.Results: Our results showed that 18β-Gly had significant cytotoxic effects and no apparent side effects. 18β-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18β-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-κB) 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 extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-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, 18β-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18β-Gly is a novel promising candidate for the treatment of lung cancer.Keywords: 18β-glycyrrhetinic acid, lung cancer, apoptosis, cell cycle arrest, ROS, cell migration

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