Functional Food Potential of Cyclic Dipeptides from Lactobacillus plantarum: Inhibition of Breast Cancer via Cancer Stem Cell Regulation

Recent studies have demonstrated that lactic acid bacteria (LAB) and their culture filtrates (CFs) can inhibit cancer progression through various mechanisms that promote apoptosis. However, there remains a paucity of experimental evidence concerning the effects of organic acid-removed LAB CFs and their secondary small metabolites, particularly in the context of non-gastrointestinal cancers. Among the metabolites produced by LAB, cyclic dipeptides (CDPs) are regarded as promising candidates for drug design due to their structural diversity and the presence of chiral side chains. Our previous research has indicated that Lactobacillus plantarum LBP-K10, isolated from kimchi, exhibits potent antimicrobial activity through the production of CDPs. Therefore, we aim to investigate the potential of CFs as CDP supplements, with a specific focus on the single CDP, cis-cyclo(L-Phe-L-Pro), in relation to breast cancer prevention. Notably, oral administration of Lb. plantarum LBP-K10 CFs has been shown to inhibit breast cancer growth in a murine model, suggesting a reduction in the stemness and self-renewal capabilities of cancer stem cells. Our research offers new insights into the anti-breast cancer properties of LAB-derived CDPs. This is substantiated by experimental evidence demonstrating both the effective absorption of CDPs in the gastrointestinal tract and their efficacy in combating breast cancer.