Modulation of FOXO3 Transcriptional Regulation by Cisplatin and Curcumin in Human Embryonic Kidney Cells
5 affiliations
- 1Facultad de Medicina, National Autonomous University of Mexico, Mexico City 04510, Mexico
- 2Unidad de Investigación y Diagnóstico en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
- 3Biobanco de Células, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
- 4Laboratorio de Inmunometabolismo, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
- 5Dirección de Investigación, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
Abstract
Cisplatin is a highly effective anti-neoplastic agent, but its clinical application is limited by its association with severe nephrotoxicity. Although extensive research has identified several mechanisms underlying cisplatin-induced nephrotoxicity, the precise molecular pathways remain incompletely understood. Recent studies have highlighted the role of intrinsic survival, senescence, and longevity signaling pathways, including those governed by the FOXO3 transcription factor. In this study, we examined the effects of cisplatin and curcumin on the DNA methylation status and mRNA expression of FOXO3 in human embryonic kidney (HEK293) cells. Our results indicate that the FOXO3 promoter is methylated in cisplatin-treated cells, and that cisplatin regulates FOXO3 transcription in a dose-dependent manner. Quantitative RT-qPCR revealed that moderate cytotoxic concentrations of cisplatin (10 and 40 µM) significantly downregulate FOXO3 mRNA. Furthermore, co-treatment with the antioxidant curcumin successfully restored and enhanced FOXO3 expression at moderate cisplatin doses (10 µM) but failed to rescue expression at high doses (40 µM). Moreover, curcumin treatment (10 µM) reverses the effects of low-dose, but not high-dose, cisplatin (40 and 60 µM). Taken together, these findings provide a foundation for understanding the epigenetic and transcriptional regulation of FOXO3 and highlight its potential as a target for antioxidant-mediated nephroprotection and its role in cell survival.
Related
- Comparison between metformin and intermittent fasting for renoprotective effects through mitophagy modulation in a rat cisplatin-induced acute kidney injury model
- Transcriptional regulation of disease-relevant microglial activation programs
- SARS-CoV-2 ORF8 Exploits Host miRNA Networks to Rewire Post-Transcriptional Regulation
- Multimodal Analysis of Transcriptional Regulation in the Dorsolateral Prefrontal Cortex Enhances Alzheimer's Disease Risk Gene Discovery
- Epigenetic regulation of the transcriptional activity of genes mediating the neuroprotective activity of ceftriaxone in the brain in a rat model of sporadic Alzheimer disease: the involvement of histone deacetylase 1.
BibTeX
@article{coronadomoreno2026modulation,
title = {{Modulation of FOXO3 Transcriptional Regulation by Cisplatin and Curcumin in Human Embryonic Kidney Cells}},
author = {Edson Coronado-Moreno and Victor Mendoza-Santos and Isabel Larre and Diana González-Cázares and Elisa Dorantes and Oscar Medina-Contreras and Adriana Sánchez-Boiso and Benjamin A. Rodriguez-Espino and Omar Guadarrama and Mara Medeiros},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208970},
url = {https://www.mdpi.com/1422-0067/27/20/8970},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Modulation of FOXO3 Transcriptional Regulation by Cisplatin and Curcumin in Human Embryonic Kidney Cells
AU - Edson Coronado-Moreno
AU - Victor Mendoza-Santos
AU - Isabel Larre
AU - Diana González-Cázares
AU - Elisa Dorantes
AU - Oscar Medina-Contreras
AU - Adriana Sánchez-Boiso
AU - Benjamin A. Rodriguez-Espino
AU - Omar Guadarrama
AU - Mara Medeiros
PY - 2026
DA - 2026/10/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208970
UR - https://www.mdpi.com/1422-0067/27/20/8970
AB - Cisplatin is a highly effective anti-neoplastic agent, but its clinical application is limited by its association with severe nephrotoxicity. Although extensive research has identified several mechanisms underlying cisplatin-induced nephrotoxicity, the precise molecular pathways remain incompletely understood. Recent studies have highlighted the role of intrinsic survival, senescence, and longevity signaling pathways, including those governed by the FOXO3 transcription factor. In this study, we examined the effects of cisplatin and curcumin on the DNA methylation status and mRNA expression of FOXO3 in human embryonic kidney (HEK293) cells. Our results indicate that the FOXO3 promoter is methylated in cisplatin-treated cells, and that cisplatin regulates FOXO3 transcription in a dose-dependent manner. Quantitative RT-qPCR revealed that moderate cytotoxic concentrations of cisplatin (10 and 40 µM) significantly downregulate FOXO3 mRNA. Furthermore, co-treatment with the antioxidant curcumin successfully restored and enhanced FOXO3 expression at moderate cisplatin doses (10 µM) but failed to rescue expression at high doses (40 µM). Moreover, curcumin treatment (10 µM) reverses the effects of low-dose, but not high-dose, cisplatin (40 and 60 µM). Taken together, these findings provide a foundation for understanding the epigenetic and transcriptional regulation of FOXO3 and highlight its potential as a target for antioxidant-mediated nephroprotection and its role in cell survival.
SN - 1422-0067
ER -