Triptonide-mediated PTGS2 Inhibition Induces Autophagic Cell Death to Suppress the Progression of Triple-negative Breast Cancer and Epithelial Ovarian Cancer
Abstract
, as a potent antitumor agent. A series of functional assays showed that TN represses proliferation in TNBC and EOC cell lines, cell-derived xenograft, and patient-derived organoid models. Through molecular docking, molecular dynamics simulation, surface plasmon resonance, cell thermal shift assay, and drug affinity reaction target stability assays, we pinpointed PTGS2 as a direct target of TN. Mechanistically, TN binds to His-207 in PTGS2 and induces proteasome degradation of PTGS2 through recruiting E3 ubiquitin-protein ligase NEDD4. TN-induced PTGS2 downregulation leads to the inhibition of the JAK/STAT3/c-Myc signaling axis, resulting in suppression of tumor proliferation and the induction of autophagic cell death. In conclusion, our findings highlight TN as a promising candidate for TNBC and EOC treatment, acting through a novel mechanism involving targeted degradation of PTGS2 protein.
Fields of Study & Subjects
Natural Compounds in Disease Treatment
Autophagy in Disease and Therapy
Cell death mechanisms and regulation
Publication details
- Journal / source
- International Journal of Biological Sciences
- Publisher
- Ivyspring International Publisher
- Volume
- 22
- Issue
- 5
- Pages
- 2215–2232
- Publication date
- 30 January 2026
- Language
- EN