Antiproliferative, selective cytotoxicity and apoptotic effect of Bacillus coagulans GBI-30 postbiotic on colorectal cancer cells

Colorectal cancer represents a significant global health burden, standing as the third most frequently diagnosed malignancy and the second leading cause of cancer-related fatalities worldwide. This highlights the urgent need for new and innovative therapeutic agents. This study aimed to investigate the anticancer effects of postbiotic derived from Bacillus coagulans GBI-30,6086 and investigate their impact on the mRNA expression of key candidate genes associated with colorectal cancer signaling networks. The postbiotic was extracted and its antimicrobial activity and physicochemical characteristics was evaluated using FTIR spectroscopy. The anti-proliferative and apoptotic effects of the postbiotic on Caco-2 (cancerous) and HDF (General non-cancerous human cell model) cells were assessed through MTT and Annexin V/PI flow cytometry assays. At the molecular level, relative mRNA expression changes across 12 candidate genes involved in apoptosis, proliferation, and inflammation were quantified using RT-qPCR, complemented by KEGG pathway mapping analysis. The postbiotic exerted dose and time dependent cytotoxic effects on Caco-2 cells while showing high biocompatibility toward healthy HDF cells. Flow cytometry confirmed a significant, selective induction of programmed cell death in malignant cells. At the transcriptomic level, postbiotic treatment significantly upregulated the tumor suppressor PTEN and the pro-apoptotic gene CASP9 , while downregulating PIK3CB , BCL2 , TLR4 , TGFB , EGFR , GLI2 , and CEACAM5 . Expression shifts for CTNNB1 , HES1 , and IL6 demonstrated downward trends without reaching statistical significance. KEGG pathway mapping confirmed the functional integration of these candidate genes within central cascades, including Pathways in cancer and Colorectal cancer. Our findings indicate that B. coagulans GBI-30 postbiotic exert selective cytotoxicity and induce apoptosis in Caco-2 cells, accompanied by distinct transcriptomic modulation of key oncogenic and inflammatory gene markers. These results highlight the biotherapeutic potential of postbiotics as a safe candidate for complementary cancer management, warranting further functional protein-level investigation.