Traditional dairy-derived Lactobacillus pentosus enhances the anticancer activity of ۵-fluorouracil against breast cancer cells

Objective(s): Breast cancer remains a significant global health challenge and a leading cause of cancer-related mortality. Probiotics, key regulators of microbial and immune homeostasis, have emerged as promising candidates for cancer prevention and therapy. This study investigated the anticancer effects of Lactobacillus-derived cell-free supernatants (CFS) in in vitro and in vivo breast cancer models.Materials and Methods: Lactobacillus strains were characterized for growth, viability, and antimicrobial activity. Standardized Lactobacillus cultures were used to prepare CFS by centrifugation and membrane filtration. The effects of CFS, alone or in combination with ۵-fluorouracil (۵-FU; ۵ mg/kg every other day), on ۴T۱ breast cancer cell proliferation, migration, apoptosis, and inflammation were evaluated using MTT, flow cytometry, qPCR, and ELISA. An in vivo ۴T۱ breast cancer mouse model was established to assess the effects of CFS on tumor growth and associated molecular and histopathological changes. Statistical analyses were performed using Student’s t-test or one-way ANOVA with Tukey’s post hoc test; P<۰.۰۵ was considered significant.Results: Co-treatment with CFS and ۵-FU inhibits cell proliferation and cell-cycle progression by modulating p۵۳ and cyclin D۱ expression (P<۰.۰۵). CFS decreases tumor growth and promotes apoptosis by regulating BCL-۲ and Bax (P<۰.۰۵). Moreover, co-treatment enhanced the inhibitory effect of ۵-FU on cancer cell migration by modulating E-cadherin, MMP۲, and MMP۹ expression (P<۰.۰۵).Conclusion: Lactobacillus-derived CFS may enhance the antiproliferative and pro-apoptotic effects of ۵-FU in breast cancer models. These findings provide a preclinical basis for further investigation into their therapeutic potential.

کلیدواژه ها:

۵-fluorouracil ، Apoptosis ، Breast Cancer ، Cell-free supernatant ، Inflammation ، Lactic acid bacterium ، Postbiotic