Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer

• Published in: Toxicology and applied pharmacology Vol. 484; p. 116842
• Main Authors: Long, Jiao, Wang, Wenjun, Chu, Jing, Li, Yueyue, Wang, Meng, Su, Jingjing, Yang, Yuting, Wang, GuoKai, Li, Qinglin, Cheng, Hui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2024
• Subjects: Animals; Arenobufagin; Bufanolides; Ferroptosis; Gastric cancer; Humans; Mice; Mice, Nude; NF-E2-Related Factor 2 - genetics; Nrf2/SLC7A11/GPX4 pathway; Reactive Oxygen Species; Stomach Neoplasms - drug therapy; Ferroptosis; Nrf2/SLC7A11/GPX4 pathway; Arenobufagin; Gastric cancer
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2024.116842

Arenobufagin (ArBu) is a natural monomer extracted and isolated from the secretion of the Chinese toad, also known as toad venom. This compound exerts anti-tumor effects by promoting apoptosis in tumor cells, inhibiting tumor angiogenesis, and preventing the invasion and migration of tumor cells. However, their impact on ferroptosis in tumor cells has yet to be fully confirmed. In this study, we established a subcutaneous transplant tumor model in nude mice to investigate the inhibitory effect of ArBu on gastric cancer cells (MGC-803) and the safety of drug delivery. in vitro experiments, we screened the most sensitive cancer cell lines using the MTT method and determined the response of ArBu to cell death. Use flow cytometry to measure cytoplasmic and lipid reactive oxygen species (ROS) levels. Determine the expression levels of ferritin-related proteins through Western blot experiments. In addition, a MGC-803 cell model overexpressing Nrf2 was created using lentiviral transfection to investigate the role of ArBu in inducing ferroptosis in cancer cells. Our research findings indicate that ArBu inhibits the proliferation of MGC-803 cells and is linked to ferroptosis. In summary, our research findings indicate that ArBu is a potential anti-gastric cancer drug that can induce ferroptosis in human cancer cells through the Nrf2/SLC7A11/GPX4 pathway.
•ArBu inhibits gastric cancer cells growth and is associated with ferroptosis.•ArBu induces ferroptosis in MGC-803 cells through the Nrf2/SLC7A11/GPX4 pathway.•Overexpression of Nrf2 reduces ArBu induced ferroptosis in MGC-803 cells.