Zeaxanthin Suppresses Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Cancer in Mice by Inhibiting Inflammation and Proliferation.
Background/Aims The treatment of colorectal cancer (CRC) remains a challenge in clinical research. Zeaxanthin (ZEA) has demonstrated substantial anti-inflammatory and anticancer effects. However, its preventive effects and underlying mechanisms in CRC remain elusive. Therefore, this study investigated the preventive effects and 10 molecular mechanisms of ZEA in CRC. Materials and Methods The effects of ZEA on tumor formation, inflammatory responses, and cell proliferation were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model of CRC. Furthermore, the anti-inflammatory and antiproliferative mechanisms of ZEA were evaluated in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and CRC cell lines (HCT116 and SW620). Results Treatment with 50 mg/kg ZEA significantly inhibited AOM/DSS-induced CRC progression. Furthermore, treatment with ZEA reduced tumor formation in the colonic lining, increased body weight, enhanced colorectal length, improved overall survival rate, and attenuated pathological changes in mice. Moreover, ZEA significantly reduced proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and Ki-67 expression levels. Mechanistically, ZEA mitigated inflammation in LPS-stimulated RAW264.7 macrophages by suppressing the nucleotide-binding oligomerization domain-containing protein 1 (NOD1)/receptor-interacting protein 2 kinase (RIP2)/ nuclear factor-κB (NF-κB) signaling pathway. In addition, it suppressed proliferation of HCT116 and SW620 cells by inhibiting the signaling pathway of PI3K/AKT/MYC. Conclusion ZEA exerted significant anti-CRC effects, including anti-inflammatory and antiproliferative actions through multitarget mechanisms, such as modulation of the NOD1/RIP2/NF-κB and PI3K/AKT/MYC signaling pathways. These findings suggest that ZEA is a promising natural chemopreventive agent for the prevention and treatment of CRC.