Jorunnamycin A induces apoptosis in pancreatic ductal adenocarcinoma cells, spheroids, and patient-derived organoids by modulating KRAS-mediated survival pathways.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis, frequently driven by oncogenic KRAS mutations. Among these, KRAS G12D is the most prevalent, contributing to chemoresistance and limiting the efficacy of current therapeutic strategies. This study investigates the therapeutic potential of jorunnamycin A (JA), a bioactive compound derived from the marine sponge Xestospongia, in PDAC. Molecular docking analyses were performed to assess JA's binding affinity for various KRAS protein variants. The synergistic effects of JA in combination with standard chemotherapeutic agents were evaluated using the Bliss independence model in pancreatic cancer cell lines and patient-derived PDAC organoids harboring distinct KRAS mutations. Furthermore, western blot anal

SUBMITTER: Khine HEE 

PROVIDER: S-EPMC11965318 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature