Eriodyctiol induces P53-dependent apoptosis in pancreatic cancer through disruption of MDM2-P53 interaction and synergistically enhances gemcitabine efficacy
Year: 2026
Type: article
Abstract: Background: Pancreatic cancer remains one of the most lethal malignancies with limited therapeutic options. This study investigates the anti-cancer effects of eriodyctiol, a natural flavonoid, and its potential as combination therapy with gemcitabine in pancreatic cancer treatment.Methods: Molecular docking analysis indicated eriodyctiol-P53 interactions. Pancreatic cancer cells BxPC-3 and Capan-2 were treated with eriodyctiol, and effects were assessed using Cell Counting Kit-8 (CCK-8) viability assays, Western blot, immunofluorescence, co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Synergistic effects with gemcitabine were evaluated in vitro and validated in xenograft mouse models.Results: Eriodyctiol demonstrated dose-dependent cytotoxicity in BxPC-3 and Capan-2 cells. Treatment enhanced P53 protein stability and nuclear translocation, upregulated downstream targets p21, BAX, and PUMA, and increased apoptosis. CETSA confirmed direct eriodyctiol-P53 binding, and Co-IP assay revealed the disruption of MDM2-P53 interaction by eriodyctiol treatment. Rescue experiments confirmed P53-dependent, caspase-3-mediated apoptosis induced by eriodyctiol. Importantly, combination with gemcitabine showed strong synergistic effects in vitro and enhanced anti-tumor efficacy in vivo.Conclusions: Eriodyctiol exhibits potent anti-cancer activity through P53 binding and MDM2-P53 interaction disruption, leading to P53-dependent apoptosis. The compound shows promise as a novel therapeutic strategy that synergistically enhances gemcitabine efficacy in pancreatic cancer treatment.
Source: Translational Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224095188