CONVERGENT MODULATION OF THE EPIGENETIC MACHINERY BY NATURAL COMPOUNDS IN LEUKEMIA MODELS
- 1Centro de Hematologia e Hemoterapia (Hemocentro), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Universidade São Francisco, Campinas, SP, Brazil
- 2Centro de Hematologia e Hemoterapia (Hemocentro), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Abstract
Background: Epigenetic dysregulation contributes to aberrant transcriptional programs in leukemia and represents a potential therapeutic target. Natural compounds can modulate components of the epigenetic machinery through different mechanisms. This study integrated findings obtained with epigallocatechin-3-gallate (EGCG), curcumin, and gallic acid to characterize convergent and compound-specific effects on DNA methylation- and histone acetylation-related pathways in leukemia models. Methods: Leukemic cell lines and U937 xenograft tumors generated in NOD/SCID mice were evaluated. Protein levels of DNMT1, DNMT3A, class I HDACs, STAT3/p-STAT3, and SHPTP2 were assessed by Western blotting. For EGCG, DNMT1 and DNMT3A mRNA levels were also measured, and chromatin immunoprecipitation was used to evaluate acetylated histone H3 and H4 enrichment at the DAPK1 and BCL2L11 promoter regions. Results: EGCG reduced DNMT1 protein levels and STAT3, while DNMT1 and DNMT3A mRNA levels remained unchanged, a pattern consistent with post-transcriptional regulation of DNMT1. Curcumin reduced DNMT1, DNMT3A, STAT3, and p-STAT3 protein levels and increased SHPTP2. At the histone deacetylase level, EGCG reduced HDAC1, HDAC2, and HDAC3, whereas gallic acid reduced HDAC1, HDAC2, HDAC3, and HDAC8 in xenograft samples. ChIP analysis after EGCG treatment showed enrichment of acetylated H3 and H4 at the DAPK1 and BCL2L11 promoter regions, providing locus-specific evidence of changes in histone acetylation. Conclusion: These findings show that the three natural compounds affect distinct but overlapping components of the epigenetic machinery, including DNMTs, STAT3/p-STAT3, class I HDACs, and promoter-associated histone acetylation. The integrated pattern supports further investigation of natural compounds as multi-level epigenetic modulators in leukemia.
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BibTeX
@article{alvarez2026convergent,
title = {{CONVERGENT MODULATION OF THE EPIGENETIC MACHINERY BY NATURAL COMPOUNDS IN LEUKEMIA MODELS}},
author = {Marisa Claudia ALVAREZ and Henriquy Aguiar COELHO and João Vitor LUZ and Karla Priscila FERRO and Irene Marisa SANTOS and Sara Teresinha Olalla SAAD},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107576},
url = {https://doi.org/10.1016/j.htct.2026.107576},
note = {CC BY},
}
RIS
TY - JOUR
TI - CONVERGENT MODULATION OF THE EPIGENETIC MACHINERY BY NATURAL COMPOUNDS IN LEUKEMIA MODELS
AU - Marisa Claudia ALVAREZ
AU - Henriquy Aguiar COELHO
AU - João Vitor LUZ
AU - Karla Priscila FERRO
AU - Irene Marisa SANTOS
AU - Sara Teresinha Olalla SAAD
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107576
UR - https://doi.org/10.1016/j.htct.2026.107576
AB - Background: Epigenetic dysregulation contributes to aberrant transcriptional programs in leukemia and represents a potential therapeutic target. Natural compounds can modulate components of the epigenetic machinery through different mechanisms. This study integrated findings obtained with epigallocatechin-3-gallate (EGCG), curcumin, and gallic acid to characterize convergent and compound-specific effects on DNA methylation- and histone acetylation-related pathways in leukemia models. Methods: Leukemic cell lines and U937 xenograft tumors generated in NOD/SCID mice were evaluated. Protein levels of DNMT1, DNMT3A, class I HDACs, STAT3/p-STAT3, and SHPTP2 were assessed by Western blotting. For EGCG, DNMT1 and DNMT3A mRNA levels were also measured, and chromatin immunoprecipitation was used to evaluate acetylated histone H3 and H4 enrichment at the DAPK1 and BCL2L11 promoter regions. Results: EGCG reduced DNMT1 protein levels and STAT3, while DNMT1 and DNMT3A mRNA levels remained unchanged, a pattern consistent with post-transcriptional regulation of DNMT1. Curcumin reduced DNMT1, DNMT3A, STAT3, and p-STAT3 protein levels and increased SHPTP2. At the histone deacetylase level, EGCG reduced HDAC1, HDAC2, and HDAC3, whereas gallic acid reduced HDAC1, HDAC2, HDAC3, and HDAC8 in xenograft samples. ChIP analysis after EGCG treatment showed enrichment of acetylated H3 and H4 at the DAPK1 and BCL2L11 promoter regions, providing locus-specific evidence of changes in histone acetylation. Conclusion: These findings show that the three natural compounds affect distinct but overlapping components of the epigenetic machinery, including DNMTs, STAT3/p-STAT3, class I HDACs, and promoter-associated histone acetylation. The integrated pattern supports further investigation of natural compounds as multi-level epigenetic modulators in leukemia.
SN - 2531-1379
SN - 2531-1387
ER -