Abstract
Increasing evidence indicates important antiproliferative and anti-inflammatory roles of brucine in various diseases. However, the mechanism through which brucine causes the cell death of gastric cancer (GC) remains unclear. In the current research, we looked into whether brucine inhibits GC progression. GC cell migration and proliferation were assessed in response to brucine using Transwell, scratch, and the Cell Counting Kit-8 (CCK-8) assays. To assess the expression of proteins linked to ferroptosis, western blotting was used. An in vivo experiment was conducted to investigate if brucine decreases tumor growth. The CCK-8 experiment demonstrated that brucine reduced AGS and MKN45 cell viability in a way that was dose- and time-dependent. Brucine dramatically promoted cell death in AGS and MKN45 cells according to flow cytometry. In addition, brucine reduced AGS and MKN45 cells' ability to migrate. According to Western blot investigations, brucine elevated p53 and ALOX12 expression, while suppressing the expression of SLC7A11 in AGS and MKN45 cells. Notably, silencing p53 reversed brucine-induced ferroptotic cell death. Additionally, brucine was shown to decrease tumor weight and volume in in vivo experiments. Moreover, malondialdehyde (MDA) and Fe2+ levels decreased in response to brucine treatment. Furthermore, in tumors treated with brucine, p53 and ALOX12 expression increased, whereas SLCA711 expression decreased. In summary, we demonstrated that brucine regulates the p53/SLCA711/ALOX12 axis to cause ferroptosis in GC cells. The results of this study lend support to the idea of treating GC with brucine.