Integrated in vitro and in silico analysis of pomegranate-derived polyphenols targeting novel variants in MCF-7 breast cancer cells.

BACKGROUND: Breast cancer remains an important health burden among people of different geographical regions worldwide, with a recorded number of cases diagnosed at approximately 2.3 million in the year 2022. METHODS: This research employed both experimental and computational methods to investigate the potential of treating ER-positive breast cancer using MCF-7 cell lines with three pomegranate-derived compounds (polyphenols), specifically ellagic acid, gallic acid, and punicalagin. RESULTS: Whole-genome sequencing of MCF-7 cells revealed key mutated genes as ESR1, EYA3, LYST, GATA3, and SLC39A12, critically involved in the pathogenesis of breast cancer. Results from in vitro studies showed that each of the compounds demonstrated both time- and dose-dependent decreases in cell viability, induced by apoptosis, as well as increases in caspase activation and reactive oxygen species levels. DISCUSSION: Significant binding affinities and interactions have been identified for ESR1, EYA3, and LYST proteins. Further elucidation of the potential mechanisms by which pomegranate components modify cancer-related pathways was performed using network analysis and pathway enrichment. CONCLUSION: This study provides scientific evidence for the components of pomegranate juice and their strategies for preventing and treating breast cancer, bridging the gap between traditional knowledge and modern evidence-based medicine.