Feronia elephantum Corrêa fruit extract attenuates DMBA-induced breast cancer in Sprague-Dawley rats; a computational and experimental pharmacology approach

Breast cancer remains a leading cause of cancer-related mortality worldwide, with therapeutic resistance and systemic toxicity limiting current treatments. Natural products are increasingly explored as safer alternatives. Feronia elephantum Corrêa, a Rutaceae fruit traditionally used in Indian medicine, is rich in phenolic compounds with reported antioxidant and antimicrobial effects. This study investigated its anticancer potential using an integrated computational-experimental approach. Bioactive phytoconstituents of F. elephantum were profiled and assessed for ADMET, drug-likeness, and predicted pharmacological activity. Protein-pathway-compound interaction networks were constructed, followed by molecular docking and molecular dynamics simulations for 200 ns via GROMACS analysing various stability parameters (RMSD, RMSF, SASA, RoG, and H bond). Cytotoxicity and migration assays were performed in MCF7, SKBR3, and T47D breast cancer cell lines. In vivo efficacy was evaluated in a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer rat model, examining tumour volume, liver and kidney biomarkers, oxidative stress parameters, and histopathology. Network pharmacology revealed norkuraniol, camptothecin, and lignan as potential bioactives acting via PI3KCA/PI3K-Akt signalling. Docking and simulation confirmed stable interactions of AKT1 and PGR with 6-O-galloylglucose and adoxosidic acid. The extract exhibited marked cytotoxicity in ER-positive cell lines (MCF7, T47D), reduced cell migration, and enhanced doxorubicin activity. In DMBA rats, extract treatment at various doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) significantly reduced tumour burden, restored hepatic and renal biomarkers, improved antioxidant status, and reversed neoplastic histopathology in a dose-dependent manner. F. elephantum fruit extract demonstrates potent anticancer and antioxidant effects through PI3K-Akt pathway modulation and PGR/AKT1 targeting. These findings support its translational potential as a complementary therapeutic agent in breast cancer management.