Exploring the mechanism of Bruceine D against cervical cancer by network pharmacology and the effect of Bruceine D on the EGFR pathway

Abstract

Cervical cancer (CC) remains a formidable challenge in oncology due to its high incidence and mortality rates. Despite recent advances in treatment, an immediate necessity exists for innovating advanced pharmacological interventions boasting augmented effectiveness. Bruceine D (BD), a quassinoid derived from the traditional Chinese medicinal plant Brucea javanica, has been demonstrated to possess notable anticancer properties against a range of malignant conditions, including lung, liver, leukemia, and pancreatic cancers. However, its specific effects on CC have not been thoroughly explored. This study sought to decode the effects of BD on CC through a combined method involving molecular docking analysis, network pharmacology, and data mining. From the PharmMapper database, we identified 58 potential targets of BD, and through GeneCards, we pinpointed 14 intersecting targets relevant to CC. A protein-protein interaction (PPI) network highlighted pivotal targets such as ESR1, HSP90AA1, ANXA5, EGFR, CASP7, and CCNA2. GO and KEGG enrichment analyses underscored significant biological processes and pathways, notably the EGFR signaling pathway. Molecular docking analysis revealed a strong binding affinity of BD to EGFR. Cell-based assays demonstrated that BD potently curtailed the viability, colony formation, adhesion, and mobility of Hela and Caski cells, escalating apoptosis in a dose-proportional manner. Supplementary evidence via western blot evaluations underscored BD’s capability to obstruct the EGFR signaling pathway. These findings suggest that BD exerts potent anticancer effects against CC through multiple mechanisms, positioning it as a promising therapeutic agent for further investigation and clinical validation.