Oleuropein Modulates ESR2/ERβ-Associated microRNA Responses and Alters 5-Fluorouracil Activity in the Ehrlich Ascites Tumor Model: An In Vivo and Ensemble Docking Study
4 affiliations
- 1Department of Medical Biology, Faculty of Medicine, Siirt University, Siirt 56100, Türkiye
- 2Biology Department, Faculty of Arts and Science, Harran University, Sanliurfa 63050, Türkiye
- 3Biology Department, College of Science, University of Raparin, Raniye 46012, Iraq
- 4Sanliurfa Youth and Sports Provincial Directorate, Sanliurfa 63210, Türkiye
Abstract
Oleuropein (OL) is widely recognized for its anticancer potential, yet its impact on chemotherapy response remains insufficiently defined. This study investigated whether OL modifies the efficacy of 5-fluorouracil (5-FU) and whether these treatment responses are accompanied by changes in ESR2/ERβ expression and associated miRNA profiles in the Ehrlich ascites tumor model. OL (150 mg/kg) was administered at different treatment schedules, alone or with 5-FU (20 mg/kg), and tumor burden, ascites formation, ESR2 mRNA, ERβ protein, miR-146a-5p and miR-155-5p expression were evaluated together with validated ERβ ensemble docking. While 5-FU markedly reduced viable tumor-cell burden, concomitant OL treatment substantially weakened this effect and restored tumor-cell numbers toward untreated levels. In contrast, OL administered at tumor initiation or prophylactically reduced ascites accumulation and produced distinct ESR2/ERβ expression profiles. OL also markedly altered chemotherapy-associated microRNA responses, suppressing the strong 5-FU-induced increase in miR-146a-5p and reducing miR-155-5p after prolonged exposure. Native-ligand redocking confirmed high reliability of the ERβ docking protocol (RMSD 0.242–0.411 Å). These findings identify a treatment-dependent interplay between OL, ERβ-associated responses, and 5-FU response, revealing that OL may exert both favorable and potentially antagonistic effects depending on therapeutic context.
Related
- MicroRNA-34b-5p Modulates Sepsis-Induced Acute Kidney Injury via the LMX1B/HIGD1A Axis: Implications for Molecular Therapeutics.
- Contemporary Management and Rechallenge Practices for 5‐Fluorouracil–Associated Cardiotoxicity: Insights From an International Cardio‐Oncology Society Survey
- microRNA-15b modulates stress-induced premature senescence in chronic doxorubicin cardiomyopathy
- Oxaliplatin and 5-Fluorouracil induce p53-p21-pRb-associated cell cycle arrest and a transient senescence-like phenotype in patient-derived low-grade serous ovarian cancer cells
- Pan-pediatric brain tumor microRNA networks define immune microenvironment states and responses to CAR T-cell therapy
BibTeX
@article{gungormez2026oleuropein,
title = {{Oleuropein Modulates ESR2/ERβ-Associated microRNA Responses and Alters 5-Fluorouracil Activity in the Ehrlich Ascites Tumor Model: An In Vivo and Ensemble Docking Study}},
author = {Cigdem Gungormez and Hatice Gumushan Aktas and Zeynep Celik and Busra Ergin and Elif Celik and Halwest Rasool Smail and Hidir Sulak},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101420},
url = {https://www.mdpi.com/2218-273X/16/10/1420},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oleuropein Modulates ESR2/ERβ-Associated microRNA Responses and Alters 5-Fluorouracil Activity in the Ehrlich Ascites Tumor Model: An In Vivo and Ensemble Docking Study
AU - Cigdem Gungormez
AU - Hatice Gumushan Aktas
AU - Zeynep Celik
AU - Busra Ergin
AU - Elif Celik
AU - Halwest Rasool Smail
AU - Hidir Sulak
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101420
UR - https://www.mdpi.com/2218-273X/16/10/1420
AB - Oleuropein (OL) is widely recognized for its anticancer potential, yet its impact on chemotherapy response remains insufficiently defined. This study investigated whether OL modifies the efficacy of 5-fluorouracil (5-FU) and whether these treatment responses are accompanied by changes in ESR2/ERβ expression and associated miRNA profiles in the Ehrlich ascites tumor model. OL (150 mg/kg) was administered at different treatment schedules, alone or with 5-FU (20 mg/kg), and tumor burden, ascites formation, ESR2 mRNA, ERβ protein, miR-146a-5p and miR-155-5p expression were evaluated together with validated ERβ ensemble docking. While 5-FU markedly reduced viable tumor-cell burden, concomitant OL treatment substantially weakened this effect and restored tumor-cell numbers toward untreated levels. In contrast, OL administered at tumor initiation or prophylactically reduced ascites accumulation and produced distinct ESR2/ERβ expression profiles. OL also markedly altered chemotherapy-associated microRNA responses, suppressing the strong 5-FU-induced increase in miR-146a-5p and reducing miR-155-5p after prolonged exposure. Native-ligand redocking confirmed high reliability of the ERβ docking protocol (RMSD 0.242–0.411 Å). These findings identify a treatment-dependent interplay between OL, ERβ-associated responses, and 5-FU response, revealing that OL may exert both favorable and potentially antagonistic effects depending on therapeutic context.
SN - 2218-273X
ER -