Low-molecular-weight metabolites from lactic acid bacteria suppress cervical cancer progression by inhibiting EMT via the Wnt/β-catenin pathway

Open Life Sci. 2026 Jan 23;21(1):20251264. doi: 10.1515/biol-2025-1264. eCollection 2026 Jan.

ABSTRACT

The study aimed to explore the effects of Lactic Acid Bacteria (LAB) supernatant on the epithelial-mesenchymal transition (EMT) of the cervical cancer cell lines HeLa, SiHa, and Hcerepic. We assessed the effect of LAB culture and its supernatant on the proliferation of these cells using the Cell Counting Kit-8 (CCK-8). Scratch assays were performed to evaluate cell migration inhibition. The supernatant was fractionated into >3 kDa and ≤3 kDa components to compare the antiproliferative and antimigratory properties of two fractions. Further, we analyzed the effect of ≤3 kDa supernatant on EMT markers and the Wnt/β-catenin pathway, as well as its effect under LiCl-induced Wnt/β-catenin activation. Grayscale values were obtained using Clinx Chemi Analysis software (ChemiScope 6000, Shanghai, China). LAB and its supernatant significantly inhibited cell proliferation, and the supernatant was more effective. The scratch assay indicated that the LAB supernatant markedly suppressed cell migration. The ≤3 kDa fraction exhibited stronger antiproliferative and antimigratory effects than the >3 kDa fraction. Mechanistically, the ≤3 kDa supernatant reversed EMT by upregulating E-cadherin and downregulating N-cadherin, Vimentin, and Snail. This fraction also inhibited the Wnt/β-catenin pathway, as evidenced by decreased Wnt1, SMAD4, and β-catenin levels, as well as suppressed Gsk-3β phosphorylation. Notably, the ≤3 kDa supernatant maintained its inhibitory effects on proliferation, migration, and EMT even when the Wnt/β-catenin pathway was activated by LiCl. In conclusion, LAB-derived low-molecular-weight metabolites hold therapeutic potential for cervical cancer. The ≤3 kDa supernatant inhibits cancer progression and metastasis by targeting the Wnt/β-catenin pathway and reversing EMT, representing a promising therapeutic approach.

PMID:41726556 | PMC:PMC12917598 | DOI:10.1515/biol-2025-1264