Eriodyctiol induces P53-dependent apoptosis in pancreatic cancer through disruption of MDM2-P53 interaction and synergistically enhances gemcitabine efficacy.
- 1Department of Gastroenterology, Guizhou Medical University Affiliated Cancer Hospital, Guiyang, China.
- 2Department of Gastroenterology, Guiyang Hospital of Guizhou Aviation Company, Guiyang, China.
- 3Department of Hematology and Oncology, The First People's Hospital of Guiyang, Guiyang, China.
Abstract
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. 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. 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. 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.
Related
- Efficacy and toxicities of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy for unresectable pancreatic cancer: a systematic review and meta-analysis
- Targeting PSMD14 increases chemotherapeutic sensitivity to gemcitabine by inhibiting the WNT/β-catenin pathway and glycolysis in pancreatic cancer.
- Reassessing standard neoadjuvant gemcitabine plus S-1 for resectable pancreatic head cancer: a retrospective cohort study.
- Surufatinib and camrelizumab plus nab-paclitaxel–gemcitabine as first-line treatment for metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study
- Long-Term Outcomes of Anatomical and Biological Borderline Resectable Pancreatic Ductal Adenocarcinoma After Gemcitabine/S-1-Based Neoadjuvant Chemoradiotherapy
BibTeX
@article{liu2026eriodyctiol,
title = {{Eriodyctiol induces P53-dependent apoptosis in pancreatic cancer through disruption of MDM2-P53 interaction and synergistically enhances gemcitabine efficacy.}},
author = {Zhe Liu and Long Yang and Xiaorong Zhu and Ting Dai and Lihui Cheng and Xiaoyan Hu},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-1541},
url = {https://europepmc.org/article/MED/42997689},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Eriodyctiol induces P53-dependent apoptosis in pancreatic cancer through disruption of MDM2-P53 interaction and synergistically enhances gemcitabine efficacy.
AU - Zhe Liu
AU - Long Yang
AU - Xiaorong Zhu
AU - Ting Dai
AU - Lihui Cheng
AU - Xiaoyan Hu
PY - 2026
DA - 2026/09/28
JO - Translational cancer research
DO - 10.21037/tcr-2026-1541
UR - https://europepmc.org/article/MED/42997689
AB - 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. 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. 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. 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.
SN - 2218-676X
SN - 2219-6803
ER -