Helminth-derived products act as an adjuvant in colitis-associated colorectal cancer 5-FU treatment by downregulating SIRT6 expression 4403

Abstract Description Colorectal cancer (CRC) is the third most common cancer and ranks second worldwide in mortality. Intrinsic and external factors, including chronic inflammation like ulcerative colitis and Crohn’s disease, influence the development of CRC. Epigenetic regulation plays a crucial role in CRC by promoting or controlling carcinogenic processes. Key mechanisms include DNA methylation, histone modification, and post-transcriptional regulation. Sirtuins (SIRT), a family of NAD-dependent histone acetylase proteins, regulate several biological processes, such as inflammation, metabolism, oxidative stress, and apoptosis. Among them, Sirtuin 6 (SIRT6) is particularly interesting in CRC. Some reports suggest that high levels of SIRT6 may be linked to poor prognosis in CRC. Here, using a mouse model of colitis-associated colorectal cancer (CAC), we tested for the adjuvant activity of Taenia crassiceps-derived molecules (TcES) in combination with 5-fluorouracil (5FU) by evaluating SIRT6 and pro-inflammatory cytokines expression in CAC mice treated with 5FU monotherapy, TcES, and combined therapy (TcES+5FU). Increased SIRT6 expression in colon tumors of untreated CAC mice was found, while TcES treatments reduced SIRT6 levels associated with low expression of pro-inflammatory cytokines like TNFa and IL-1b and a lower burden of colonic tumors. Thus, TcES negatively regulates SIRT6 expression, which may favor inflammation and play a role in CAC development and resistance to chemotherapy. Funding Sources DGAPA-PAPIIT IN-212722, IV200425, COMECYT CS000132 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)