The Allium cepa Derived Compound Propyl Propane Thiosulfonate (PTSO) Improves Tumorigenesis Due to Its Immunomodulatory Effect: A Preclinical Study.

Allium-derived organosulfur compounds offer significant health benefits. Specifically, PTSO, an organosulfur compound extracted from Allium cepa, has demonstrated immunomodulatory and prebiotic properties. However, its effects on tumorigenesis and gut dysbiosis in colitis-associated colorectal cancer (CAC) remain unexplored. This study aimed to investigate the impact of two PTSO formulations, free (FP) and encapsulated (EP), on a murine model of CAC focusing on their impact on the immune system and gut microbiome. The antitumor effect of PTSO was characterized in vitro in HCT116 cells and in a CAC murine model induced by the administration of azoxymethane and dextran sulfate sodium. FP and EP were administered orally throughout the assay and 5-fluorouracil was used as a control. FP and EP were effective in reducing tumor burden, with EP showing a greater positive impact on tumorigenesis by reducing both tumor number and size, likely due to enhanced bioavailability. PTSO induced apoptosis through oxidative stress mechanisms and modulated key pathways like STAT3, PI3K/mTOR, and Wnt/β-catenin. Additionally, PTSO, especially EP, exhibited an immunomodulatory effect on myeloid and lymphoid populations and hindered the release of cytokines that prompted inflammation and cancer progression. PTSO also enhanced gut barrier integrity, increased the abundance of beneficial bacteria, like Akkermansia, Leuconostoc mesenteroides, and Weissella confusa, and the release of short-chain fatty acids (SCFAs). This study highlights the potential of PTSO, particularly in its encapsulated form, as a promising therapeutic agent for CRC by targeting both tumor growth and the underlying inflammatory processes while restoring gut microbiota balance.