Eupalinolide B suppresses pancreatic cancer by ROS generation and potential cuproptosis.

ABSTRACT

Pancreatic cancer is highly lethal with limited effective treatments. This study explores the therapeutic effects of eupalinolide B (EB) from Eupatorium lindleyanum DC on pancreatic cancer cells. Through cellular functional assays, we observed that EB effectively inhibits cell viability, proliferation, migration, and invasion. In a xenograft mouse model, EB treatment resulted in reduced pancreatic cancer tumor growth and decreased expression of Ki-67. Mechanistically, EB induces apoptosis, elevates reactive oxygen species (ROS) levels, and disrupts copper homeostasis. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) identified copper ion binding pathways and potential involvement in cuproptosis. Furthermore, EB enhances the cytotoxic effects of elesclomol (ES), increasing ROS levels in a copper-dependent manner and exhibiting synergistic cytotoxicity. These findings suggest that EB, either alone or in combination with ES, represents a promising strategy for targeting metal ion dysregulation and inducing potential cuproptosis in pancreatic cancer, offering a potential improvement in therapeutic outcomes.