Brucein D suppresses breast cancer proliferation and migration via targeting the FAK/LRG1 signaling pathway

Background Breast cancer (BC) ranks as one of the most prevalent cancers in women globally and stands as a primary cause of cancer-induced death. The scarcity of effective BC treatments prompts the urgent need for innovative therapeutic approaches and new agents. Focal adhesion kinase (FAK), a critical non-receptor intracellular tyrosine kinase, has garnered significant attention as a viable target for cancer therapy. Bruceine D (BD), an active compound isolated from Brucea javanica , has demonstrated efficacy in inhibiting the proliferation of various cancer cells. However, its impact on BC through FAK modulation has not been established. Methods The MTT and transwell were used to determine the cell proliferation and migration ability. Furthermore, mitochondrial biological function is assayed by ROS release, ATP production, and mitochondrial membrane potential. In addition, RNA-seq explored the involvement of FAK in regulating the LRG1 signaling pathway and revealed its role in mediating apoptosis in BC cells. Results The experimental results revealed that BD exerted remarkable inhibitory effects on BC cell proliferation and migration. Furthermore, BD treatment induced substantial metabolic alterations in BC cells, characterized by reduced ATP production, increased ROS accumulation, and decreased MMP. Clinical research demonstrated significantly elevated FAK expression levels in BC patient tissue samples, highlighting its potential as a promising therapeutic target. Mechanistic investigations elucidated that BD exerts its anti-cancer effects through dual modulation of FAK/LRG1 signaling pathway, ultimately triggering apoptotic cell death in BC cells. Conclusion These results elucidate a potential mechanism of BD action and underscore its promise as a small-molecule FAK inhibitor, potentially valuable in BC treatment.