Targeting IL-1beta signalling in cervical cancer with zerumbone: evidence from experimental and computational studies

Zerumbone (ZER), a bioactive sesquiterpene present in Zingiber zerumbet, has been extensively reported to have anticancer and anti-inflammatory potential. This study aimed to examine the impact of ZER on interleukin-1 beta (IL-1Beta) in HeLa cervical cancer cells. Increasing concentrations of ZER (1-40 μM) were added to the cultures every 24 h, and the level of IL-1Beta in the culture supernatants was measured by an ELISA-based assay. The concentration of IL-1β decreased with increasing ZER concentration. Molecular docking study also showed that ZER binds favourably to IL-1Beta, with a MolDock score of −209.92, indicating stable interactions with key residues, which was also verified by 100 ns molecular dynamics (MD) simulations, suggesting stable RMSD, radius of gyration (Rg), and solvent-accessible surface area (SASA) profiles. These results indicate that zerumbone treatment is associated with reduced extracellular IL-1Beta levels in HeLa-cell culture and that zerumbone can interact with IL-1Beta at the molecular level. However, because an induced inflammatory model, pathway-inhibitor controls, and time-course analysis were not performed, the present findings do not establish direct suppression of actively induced IL-1Beta production or a specific IL-1Beta/NF-κB-mediated mechanism.