Beyond DNA Demethylation: Curcumin as a Context-Dependent Remodeler of the Epigenetic Landscape
- 1Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Biologia Cellulare, Università di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy
- 2Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), 90146 Palermo, Italy
Abstract
Curcumin has attracted considerable attention for its pleiotropic effects on cellular signaling, inflammation, metabolism, and cancer biology. A growing body of evidence indicates that these effects coincide with alterations in the epigenetic landscape; however, a causal contribution of such alterations has seldom been established experimentally. Although curcumin has frequently been described as an epigenetic demethylating agent, accumulating evidence suggests more complex, context-dependent mechanisms, which involve DNA methylation, hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs. These changes may affect the accessibility and transcriptional activity of genes involved in cell identity, proliferation, differentiation, inflammation, and therapeutic response. The few genome-wide methylomic and transcriptomic studies available, mostly performed in a single cell line and at micromolar concentrations that exceed those reached in vivo, suggest that curcumin-induced epigenetic changes depend on cellular context, dose, and exposure conditions. This narrative review summarizes evidence published mainly from 2004 onward on the effects of curcumin on DNA methylation and hydroxymethylation, while integrating its interactions with histone modifications, chromatin organization, and non-coding RNA networks. We further discuss how these interconnected mechanisms contribute to the rewiring of gene regulatory programs and may underlie the biological and therapeutic effects of curcumin. Finally, we highlight the current limitations, including the poor bioavailability of curcumin, the non-specific chemistry of the molecule, and the scarcity of integrative multi-omics data, and we discuss what would be required to establish whether curcumin-induced epigenetic changes are relevant at pharmacologically attainable concentrations.
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BibTeX
@article{costa2026beyond,
title = {{Beyond DNA Demethylation: Curcumin as a Context-Dependent Remodeler of the Epigenetic Landscape}},
author = {Salvatore Costa and Maria Antonietta Ragusa and Aldo Nicosia},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219672},
url = {https://www.mdpi.com/1422-0067/27/21/9672},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond DNA Demethylation: Curcumin as a Context-Dependent Remodeler of the Epigenetic Landscape
AU - Salvatore Costa
AU - Maria Antonietta Ragusa
AU - Aldo Nicosia
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219672
UR - https://www.mdpi.com/1422-0067/27/21/9672
AB - Curcumin has attracted considerable attention for its pleiotropic effects on cellular signaling, inflammation, metabolism, and cancer biology. A growing body of evidence indicates that these effects coincide with alterations in the epigenetic landscape; however, a causal contribution of such alterations has seldom been established experimentally. Although curcumin has frequently been described as an epigenetic demethylating agent, accumulating evidence suggests more complex, context-dependent mechanisms, which involve DNA methylation, hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs. These changes may affect the accessibility and transcriptional activity of genes involved in cell identity, proliferation, differentiation, inflammation, and therapeutic response. The few genome-wide methylomic and transcriptomic studies available, mostly performed in a single cell line and at micromolar concentrations that exceed those reached in vivo, suggest that curcumin-induced epigenetic changes depend on cellular context, dose, and exposure conditions. This narrative review summarizes evidence published mainly from 2004 onward on the effects of curcumin on DNA methylation and hydroxymethylation, while integrating its interactions with histone modifications, chromatin organization, and non-coding RNA networks. We further discuss how these interconnected mechanisms contribute to the rewiring of gene regulatory programs and may underlie the biological and therapeutic effects of curcumin. Finally, we highlight the current limitations, including the poor bioavailability of curcumin, the non-specific chemistry of the molecule, and the scarcity of integrative multi-omics data, and we discuss what would be required to establish whether curcumin-induced epigenetic changes are relevant at pharmacologically attainable concentrations.
SN - 1422-0067
ER -