Cell-free OC01 Supernatant Suppresses IL-6-induced Proliferation and Invasion of Human Colorectal Cancer Cells: Effect on β-Catenin Degradation and Induction of Autophagy

Background And Aim: Gut microbiota is considered as a complex organ of human body. The interaction between the host and microbiota is dynamic and controlled by a huge number of factors, such as lifestyle, geography, pharmaceuticals, diet, and stress. The breakdown of this relationship could change microbiota composition favoring the onset of several diseases, including cancer. Metabolites released by microbiota bacterial strains have been reported to elicit protective effects on the mucosa that could contrast cancer development and progression. Here, we tested the ability of specific probiotic strain OC01-derived metabolites (NCIMB 30624) to contrast the malignant features of colorectal cancer (CRC) cells.

Experimental Procedure: The study was performed on two cell lines, HCT116 and HT29, cultured in 2D and 3D, and focused on the hallmarks of cell proliferation and migration.

Results And Conclusion: Probiotic metabolites reduced cell proliferation both in 2D and 3D-spheroid cultures, the latter model mimicking the growth . The bacterial metabolites also contrasted the pro-growth and pro-migratory activity of inteurleukin-6 (IL-6), an inflammatory cytokine abundantly found in the tumor microenvironment of CRC. These effects were associated with inhibition of the ERK and of the mTOR/p70S6k pathways and with the inhibition of the E-to N-Cadherin switch. In a parallel study, we found that sodium butyrate (a representative of the main probiotic metabolites) induced autophagy and β-Catenin degradation, which is consistent with the growth inhibitory activity. The present data indicate that the metabolites of OC01 (NCIMB 30624) elicits anti-tumor effect and support its possible inclusion as adjuvant therapy of CRC for limiting cancer growth and progression.