Targeting IL-10–mediated JAK–STAT signaling in cervical cancer: integrative network pharmacology, molecular docking, and experimental validation of Zerumbone

Abstract

This study investigated the potential interaction between zerumbone (ZER) and interleukin-10 (IL-10) using molecular docking and molecular dynamics (MD) simulations. Computational analyses suggested a stable association of ZER with a functionally relevant region of IL-10. Gene Ontology (GO) and pathway enrichment analyses using STRING and KEGG identified IL-10’s primary involvement in the JAK-STAT signaling pathway, which regulates immune system homeostasis, inflammation, and cellular life. Zerumbone treatment was associated with reduced IL-10 levels and modulation of downstream signaling-associated markers, including Cyclin D1 and Bcl-xL. Cell-based assays have also corroborated dose-dependent modulation of IL-10 release in HeLa cells. There was a decrease in IL-10 concentration from 70.81 pg/mL at 1 µM to 6.32 pg/mL at 40 µM of ZER. The observed suppression of IL-10 and its target genes suggests that ZER modulates the apoptotic and proliferative signaling pathways, resulting in strong anticancer activity via the IL-10 pathway.