Brucine Inhibits Gastric Cancer via Activation of Ferroptosis Through Regulating the NF‐κB Signaling Pathway

作者：Bo Zhang, Changwei Yu, Sisi Zhang, Min Zhang · 发表于：Journal of Biochemical and Molecular Toxicology · 年份：2025 · DOI：10.1002/jbt.70479 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Berberine and alkaloids research

Gastric cancer (GC) is the third leading cause of cancer mortality globally, often presenting with insidious symptoms that lead to late-stage diagnoses, underscoring the critical need for innovative diagnostic and therapeutic strategies. One such avenue is the exploration of ferroptosis, a regulated form of cell death implicated in various pathological conditions and malignancies. In this study, we demonstrate that brucine, an alkaloid derived from Strychnos nux-vomica, exerts significant antitumor effects on GC cells both in vitro and in vivo. Brucine treatment dose-dependently inhibits proliferation, migration, and invasion, and induces apoptosis and ferroptosis. Specifically, brucine treatment diminished cell viability, DNA synthesis, and colony formation, increased the expression of proapoptotic markers such as Bax, and decreased the expression of antiapoptotic Bcl-2. Additionally, brucine inhibited migration and invasion by modulating epithelial-mesenchymal transition markers. In ferroptosis assays, brucine potentiated the effects of the ferroptosis inducer Erastin, elevating levels of intracellular iron, malondialdehyde, and reactive oxygen species, while reducing glutathione levels. In vivo experiments showed that brucine markedly reduced tumor growth and modified the expression of key biomarkers in a xenograft model. Furthermore, our findings suggest that brucine's effects on cancer cell behavior and ferroptosis are associated with suppression of the NF-κB signaling p...