Concentration-Associated DNA Methylation Remodeling of Oncogenic Signaling Networks Following Moringa oleifera Treatment in Metastatic PC3 Prostate Cancer Cells
Year: 2026
Type: article
Abstract: PC3 prostate cancer (PCa) cells exhibit high metastatic potential, androgen independence, and activation of multiple oncogenic signaling pathways. Although Moringa oleifera exhibits recognized anticancer properties, its epigenetic effects in aggressive PCa remain largely unexplored. In this study, PC3 cells were treated with Moringa oleifera extract at 100 or 200 μg/mL, and its effects were assessed through functional and molecular analyses together with genome-wide DNA methylation profiling. Both concentrations increased apoptosis and reduced ERK1/2 and AKT activation, epithelial-mesenchymal transition markers, and invasion-associated molecules. Genome-wide methylation profiling revealed concentration-dependent changes in the biological pathways affected by Moringa oleifera treatment. At 100 μg/mL, hypermethylated DMR-associated genes were mainly enriched in pathways related to small GTPase signaling, focal adhesion, cytoskeletal organization, axon guidance, MAPK, Rap1 and RHO signaling. At 200 μg/mL, the enrichment profile shifted towards pathways involving cell adhesion, Wnt signalling, RAC1/CDC42 activity, and VEGF/VEGFR2-mediated angiogenesis. Hypomethylated DMR-associated genes showed a distinct, although partly overlapping, pattern of pathway enrichment. Direct comparison of the two concentrations demonstrated a preferential hypermethylation response at 200 μg/mL, particularly involving axon guidance, focal adhesion, actin-cytoskeleton regulation, MAPK and EPH–Ephrin signaling, whereas hypomethylated Reactome pathways were mainly related to NOTCH and RHOB/RHOC signaling. Collectively, these findings support Moringa oleifera as a natural multi-target epigenetic modulator capable of inducing coordinated DNA methylation remodeling in genes associated with multiple signaling networks implicated in metastatic PCa.
DOI: 10.3390/ijms27209144
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7203920090