LAUSR

Simple Summary Probiotics and their metabolites are very important for human health. The aim of this research was to determine probiotic strains with the strongest inhibitory properties against intestinal cancer cells. As a result of the screening, it was possible to find two strains, i.e., Lactiplantibacillus plantarum 0991 and Levilactobacillus brevis 0983, that could inhibit the proliferation of cancer cells by induction of oxidative stress and programmed cell death. Both strains exhibit interesting anticancer properties and potential as functional food ingredients; however, the results must be confirmed in further research. Abstract Background: Lactic acid bacteria (LAB), many of which are probiotics, can produce health-promoting metabolites (postbiotics). Purpose: To assess the mechanism of antiproliferative action of postbiotics, post-fermentation media (PFM) and cell extracts (CEs) of several strains of LAB were studied against colon (Caco-2), and cervix (HeLa) cancer cell lines, as well as normal intestine (IEC-6) cells, were used as a comparison. Methods: Postbiotics of various LAB (n = 39) were screened for their antiproliferative activity. The effect of PFM and CEs on reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP production, phosphatidylserine (PS) externalisation, and apoptosis-related caspases 3/7 and 9 activation was assayed. Results: PFM and CEs showed strong dose-dependent antiproliferative activity against Caco-2 cells, up to 77.8 ± 0.8% and 58.4 ± 1.6% for PFM and CEs, respectively. Stronger inhibitory activity against cancerous (Caco-2 and HeLa) cells than against normal (IEC-6) cells was observed. PFM were more inhibitory than CEs, and both generated oxidative stress in Caco-2 cells. PFM of L. plantarum 0991 and L. brevis 0983 induced apoptosis in Caco-2 cells by the mitochondrial signalling pathway. Conclusions: Anticancer activity of PFM and CEs of LAB, as well as the ability of apoptosis induction, is strain-specific.