Deciphering the Anticancer Potential of Bifidobacterium longum MB BBLM15 Derived Postbiotic Metabolites in Cervical Cancer: In Vitro, In Silico, and Synergy Studies.

Probiotics are beneficial microorganisms that exert several health-promoting effects, while their metabolites, referred to as postbiotics, have recently gained increasing attention for their therapeutic relevance. The present study elucidates the anticancer potential of Bifidobacterium longum MB BBLM15-derived postbiotic metabolites through an integrated experimental and computational approach. Postbiotic metabolites were extracted from Bifidobacterium longum MB BBLM15 using three different solvents (hexane, dichloromethane, ethyl acetate) and subsequently subjected to metabolic profiling. The cytotoxic potential of the three extracts was assessed against cervical cancer cells (HeLa) using a cell viability assay. Hexane-extracted postbiotic metabolites (HX-PM) showed the most potent cytotoxic activity (IC50 value 263.6 ± 1.32 µg/ml) against HeLa cells, while exhibiting less cytotoxic (IC50 value 1363 ± 7.4 µg/ml) effect towards the normal kidney epithelial cells (HEK 293), with a selectivity index of HX-PM of 5.8. The anticancer mechanism of HX-PM was further evaluated through a series of cell-based assays, which reveal that HX-PM exhibits anti-proliferative effects, induces G2/M phase cell cycle arrest, triggers apoptosis, suppresses metastasis, and modulates the intracellular redox status in the cervical cancer cells. GC-MS profiling revealed the presence of multiple bioactive metabolites in HX-PM. To further understand the intracellular mode of action, an in-silico framework encompassing network pharmacology and molecular docking was carried out, which identified PTGS2, PPARG, and MAPK3 as the top three hub candidates, with PTGS2 being the probable key molecular target. Additionally, the postbiotic metabolites demonstrated a synergistic interaction with a standard chemotherapeutic drug, cisplatin, as determined by the Chou-Talalay method, highlighting their prospective role in the adjuvant therapy of cervical cancer. Collectively, this study establishes Bifidobacterium longum MB BBLM15-derived postbiotic metabolites as effective anticancer modulators with considerable therapeutic promise.