Tyramine promotes colon cancer risk and development by inducing DNA damage and inflammation

Abstract

AbstractHigh dietary consumption of processed meat is associated with increased colorectal cancer (CRC) risk, but mechanistic links remain largely unknown. Tyramine is a biogenic amine found in processed food and a gut bacterial product from tyrosine. However, the impact of tyramine on gut health has not been studied. We found that tyramine induced necrosis and promoted cell proliferation and DNA damage in HCT116 cells. Ingestion of tyramine increased colonic tumor size, intestinal cell proliferation and inflammation (e.g., increased mRNA expression of IL-17A and a higher number of Ly6G+ neutrophils) inApcMin/+mice. Furthermore, tyramine-treated wild-type mice exhibited visible adenomas and significantly enhanced intestinal tissue DNA damage, together with altered gene pathways involved in epithelial barrier function. In addition, natural killer cell numbers were lower and polymorphonuclear-myeloid derived suppressor cells were higher in tumors from tyramine-treatedApcMin/+mice, suggesting a suppressive anti-tumor immune response. Thus, tyramine not only increases CRC risk, but also facilitates tumor development. Modulating the levels of tyramine in food and monitoring high-risk individuals could aid in better prognosis and management of CRC.