Investigating Vitamin D3's anticancer mechanisms in MCF-7 cells: a network pharmacology and omics technology approach.

Abstract

Breast cancer is one of the leading reasons of mortality due to cancer globally. Estrogen receptor-positive (ER +) breast cancer being a significant subtype. The therapeutic potential of Vitamin D₃ in cancer treatment has gained attention due to its ability to modulate key molecular targets and signaling pathways. This study investigates the anticancer mechanisms of Vitamin D₃ in MCF-7 breast cancer cells using network pharmacology and omics technology approach. Utilizing protein-protein interaction (PPI) networks, we identified several critical protein targets involved in breast cancer progression, including ESR1, ESR2, PGR, IGF1R, and KDR. Pathway enrichment analyses highlighted Vitamin D₃'s impact on pivotal signaling pathways such as the PI3K/Akt pathway, estrogen receptor signaling, and apoptosis regulation. In vitro studies showed that Vitamin D₃ significantly inhibited cell proliferation in MCF-7 cells. It also induced apoptosis and disrupted mitochondrial function. Flow cytometry analysis demonstrated a dose-dependent increase in apoptotic cell death and S-phase cell cycle arrest. Confocal imaging and mitochondrial membrane potential assays further supported the findings, indicating mitochondrial dysfunction and chromatin condensation. Additionally, gene expression analysis in breast invasive carcinoma tissues confirmed the relevance of ESR1 and PGR in hormone receptor-positive breast cancer. Histopathological studies on DMBA-induced mammary carcinoma revealed Vitamin D₃'s protective effects, reducing tumor malignancy severity through anti-proliferative and pro-apoptotic actions. These findings provide strong evidence for Vitamin D₃'s potential as a multi-targeted therapeutic agent in breast cancer, suggesting further investigation into its clinical applications and combination strategies with existing therapies as an adjunct or alternative in the treatment.