OncoTargets and Therapy (Apr 2021)

Calycosin Induces Gastric Cancer Cell Apoptosis via the ROS-Mediated MAPK/STAT3/NF-κB Pathway

  • Zhang Y,
  • Zhang JQ,
  • Zhang T,
  • Xue H,
  • Zuo WB,
  • Li YN,
  • Zhao Y,
  • Sun G,
  • Fu ZR,
  • Zhang Q,
  • Zhao X,
  • Teng Y,
  • Wang AQ,
  • Li JZ,
  • Wang Y,
  • Jin CH

Journal volume & issue
Vol. Volume 14
pp. 2505 – 2517

Abstract

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Yu Zhang,1,* Jian-Qiang Zhang,2,3,* Tong Zhang,1 Hui Xue,1 Wen-Bo Zuo,1 Yan-Nan Li,1 Yue Zhao,1 Geng Sun,1 Zhong-Ren Fu,1 Qing Zhang,1 Xue Zhao,1 Yue Teng,1 An-Qi Wang,1 Jia-Zhu Li,1 Ying Wang,4,5 Cheng-Hao Jin1,4,5 1Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China; 2Department of Food Science and Technology, College of Food Science, Northeast Agricultural University, Harbin, People’s Republic of China; 3Heilongjiang Heyi Dairy Technology Co. Ltd., Daqing, People’s Republic of China; 4Department of Food Science and Engineering, College of Food Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China; 5National Coarse Cereals Engineering Research Center, Daqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng-Hao JinDepartment of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, 5 Xinfa Street, Daqing, Heilongjiang, 163319, People’s Republic of ChinaEmail [email protected] WangDepartment of Food Science and Engineering, College of Food Science & Technology, Heilongjiang Bayi Agricultural University, 5 Xinfa Street, Daqing, Heilongjiang, 163319, People’s Republic of ChinaEmail [email protected]: Calycosin, an active compound in plants, can promote the apoptosis of various cancer cells; however, the mechanism by which it regulates reactive oxygen species (ROS) in gastric cancer (GC) cells remains unclear.Purpose: In this study, we investigated the effects of calycosin on apoptosis, the cell cycle, and migration in GC cells under ROS regulation.Results: The results of the Cell Counting Kit-8 assay suggested that calycosin had significant cytotoxic effects on 12 gastric cancer cells, but no significant cytotoxic effects on normal cells. Hoechst 33342/propidium iodide (PI) double staining and flow cytometry showed that calycosin had clear pro-apoptotic effects on AGS cells. Western blotting revealed that the expression of cytochrome C and pro-apoptotic proteins B-cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad), cleaved (cle)-caspase-3, and cle-poly (ADP-ribose) polymerase gradually increased, and the expression of anti-apoptotic protein Bcl-2 gradually decreased. Calycosin also decreased the expression of extracellular signal-regulated kinase, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation levels of p38, c-Jun N-terminal kinase, and inhibitor of NF-κB. In addition, calycosin markedly increased ROS accumulation, and pretreatment with active oxygen scavenger n-acetyl-l-cysteine (NAC) clearly inhibited apoptosis. Calycosin downregulated the cell cycle proteins cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, and cyclin E; upregulated p21 and p27; and arrested cells in the G0/G1 phase. Similarly, calycosin also downregulated Snail family transcriptional repressor 1, E-cadherin, and β-catenin and inhibited cell migration. However, pretreatment with NAC inhibited the calycosin-induced effects of cycle arrest and migration.Conclusion: In summary, calycosin induces apoptosis via ROS-mediated MAPK/STAT3/NF-κB pathways, thereby exerting its anti-carcinogenic functions in GC cells.Keywords: calycosin, human gastric cancer, apoptosis, cell cycle, cell migration, reactive oxygen species

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