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 (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options and poor prognosis. DNA methyltransferase 1 (DNMT1) maintains aberrant silencing of tumor suppressor genes, contributing to cancer progression. Our previous work demonstrated that Lantana camara leaf extract induces G0/G1 arrest and apoptosis, while inhibiting migration in MDA-MB-231 TNBC cells (Pal et al., 2024).
Purpose
This study investigated the role of DNMT1 in mediating the anticancer effects of Lantana camara extract.
Study Design
An in vitro experimental study was performed using MDA-MB-231 TNBC cells.
Methods
Cells were treated with the extract, and the expression of DNMT1 was analyzed at the mRNA and protein levels. Expression of tumor suppressor genes was assessed at mRNA level. Functional assays were conducted following DNMT1 overexpression to examine its impact on extract-induced effects. Expression of methyl-CpG binding domain protein 2 (MBD2), histone deacetylase 1 (HDAC1), and histone deacetylase 2 (HDAC2) was evaluated at the mRNA level.
Results
The extract significantly downregulated DNMT1, resulting in the reactivation of multiple tumor suppressor genes. Overexpression of DNMT1 counteracted the extract-induced reduction in cell viability, reduced G0/G1 arrest, attenuated apoptosis, and enhanced migratory capacity, while suppressing the mRNA expression of tumor suppressor genes. Additionally, the extract downregulated the mRNA expression of MBD2, HDAC1, and HDAC2, 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.
