Conventional chemotherapeutic regimens used in cervical cancer management are frequently associated with considerable adverse effects on the human body. Consequently, increasing attention has been directed toward microbial-derived bioactive compounds, particularly postbiotics, as alternative therapeutic options for malignant disorders. The present study explored the underlying mechanisms associated with two promising postbiotic-producing Lactobacillus isolates, Lactobacillus fermentum CH and L. fermentum KH, obtained from traditional Iranian dairy products. Identification of the isolates was achieved using 16S rDNA sequencing, followed by morphological and biochemical characterization. The biological effects of the derived postbiotics on a cervical cancer model were evaluated using cytotoxicity assays and apoptosis analyses. Furthermore, anticancer activity was examined by quantitative real-time PCR (qPCR) and subsequently validated through flow cytometry. The findings demonstrated that these postbiotics exerted notable anticancer effects on HeLa cells by upregulating the expression of BAX, caspase8, and caspase9, while downregulating BCl-2, IKB (Inhibitor of nuclear factor kappa-B), and RelA. Collectively, these results indicate that postbiotic derivatives from Lactobacillus strains isolated from indigenous Iranian dairy products may represent a potential topical therapeutic approach with a favorable therapeutic index for the treatment of cervical malignancy.
