Eupalinolide B suppresses pancreatic cancer by ROS generation and potential cuproptosis
Qingtian Huang,
Jie Yang,
Jiaxing Zhang,
Leyi Yao,
Baoyi Jiang,
Siyuan Du,
Fengjin Li,
Qian Peng,
Lingsha Qin,
Yanfen Wang,
Ling Qi
Affiliations
Qingtian Huang
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China; Department of Pathology, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Jie Yang
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Jiaxing Zhang
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Leyi Yao
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Baoyi Jiang
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Siyuan Du
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Fengjin Li
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Qian Peng
Biological Sample Resource Centre, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Lingsha Qin
Biological Sample Resource Centre, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China
Yanfen Wang
Department of Pathology, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China; Corresponding author
Ling Qi
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China; Biological Sample Resource Centre, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China; Division of Gastroenterology, Institute of Digestive Disease, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China; Corresponding author
Summary: 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.
