Lantana camara leaf extract-mediated suppression of DNA methyltransferase 1 promotes G0/G1 cell cycle arrest and apoptosis, and impedes migration in MDA-MB-231 triple-negative breast cancer cells
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Background
Triple-negative breast cancer is an aggressive subtype of breast cancer with a poor prognosis and limited therapeutic options. DNA methyltransferase 1 maintains aberrant silencing of tumor suppressor genes, contributing to cancer progression. Our previous work showed that Lantana camara leaf ethanolic extract induces G0/G1 arrest, apoptosis, and inhibits migration in MDA-MB-231 triple-negative breast cancer cells.
Purpose
This study investigated the role of DNA methyltransferase 1 in mediating the anticancer effects of Lantana camara extract.
Study Design
An in vitro experimental study was performed using MDA-MB-231 triple-negative breast cancer cells.
Methods
Cells were treated with the extract, and the expression of DNA methyltransferase 1 was analyzed at mRNA and protein levels. Tumor suppressor gene expression was assessed at the mRNA level, and functional assays were conducted following DNMT1 overexpression to examine its impact on extract-induced effects. Expression of methyl-CpG binding domain protein 2, histone deacetylase 1, and histone deacetylase 2 was also evaluated at the mRNA level.
Results
The extract significantly downregulated DNA methyltransferase 1, resulting in the reactivation of multiple tumor suppressor genes. Overexpression of DNA methyltransferase 1 reduced extract-induced G0/G1 arrest, attenuated apoptosis, and restored migration, while suppressing tumor suppressor gene expression. Additionally, the extract downregulated methyl-CpG binding domain protein 2, histone deacetylase 1, and histone deacetylase 2, suggesting broader modulation of epigenetic regulators.
Conclusion
Suppression of DNMT1 is a central mechanism underlying the anticancer activity of Lantana camara extract. These findings highlight its potential as a natural epigenetic modulator and a promising therapeutic candidate for TNBC.
