Alantolactone induces gastric cancer BGC-823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway

• Published in: Oncology letters 2019-06, Vol.17 (6), p.4795-4802
• Main Authors: Zhang, Xin, Zhang, Hong-Ming
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Apoptosis; Bioengineering; Breast cancer; Cancer; Cancer cells; Cancer therapies; Cancer treatment; Caprolactone; Care and treatment; Cell cycle; Cervical cancer; Chemotherapy; Cyclin-dependent kinases; Cystine; Experiments; Flow cytometry; Gastric cancer; Genetic aspects; Kinases; Oncology; Patient outcomes; Protein kinases; Proteins; Reactive oxygen species; Risk factors; Software; Stomach cancer; Studies
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2019.10172

Alantolactone (ALT), a natural sesquiterpene lactone, has been suggested to exert anti-cancer activities in various cancer cell lines. However, the effects and mechanisms of action of ALT in human gastric cancer remains to be elucidated. In the present study, the effects of ALT on BGC-823 cells were examined and the underlying molecular mechanisms associated with these effects were investigated. Cell viability was detected by using an MTT assay. Cell cycle, cell apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression levels of proteins of interest were analyzed by western blot assay. The results demonstrated that ALT triggered apoptosis and induced G0/G1 phase arrest in a dose-dependent manner. Furthermore, the expression level of the anti-apoptosis protein Bcl-2 was downregulated, and expression of the pro-apoptosis proteins Bax and cleaved PARP were significantly upregulated. The cell cycle-associated proteins cyclin-dependent kinase inhibitor 1 and cyclin-dependent kinase inhibitor 1B were also increased, while cyclin D1 was deceased. In addition, ALT induced apoptosis via the inhibition of RAC-alpha serine/threonine-protein kinase (AKT) signaling and ROS generation, which was effectively inhibited by the ROS scavenger, N-acetyl cysteine. Therefore, the results from the present study indicated that the ROS-mediated inhibition of the AKT signaling pathway serves an important role in ALT-induced apoptosis in BGC-823 cells. In conclusion, the results demonstrated that ALT exerted significant anti-cancer effects against gastric cancer cells .