L-theanine's therapeutic effects on colorectal cancer: Mechanistic insights from a 1,2-dimethylhydrazine-induced rat model

This study aimed to elucidate the novel effects and underlying mechanisms of L-theanine on colorectal cancer (CRC) in a rat model. Specifically, it focused on how L-theanine uniquely impacts cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), oxidative stress, inflammation, intestinal microbiota, and short-chain fatty acids in rat CRC compared to existing studies. In the 1,2-dimethylhydrazine (DMH) group, serum levels of CRP, AFP, CEA, and CA199 were elevated compared to controls, but L-theanine treatment reduced these levels. IHC analysis showed a significant decrease in Ki67-positive cells in colon tissues with L-theanine. HE staining indicated improved colon pathology, and TUNEL assays revealed increased apoptosis. Western blotting demonstrated up-regulation of caspase-3, cleaved caspase-3, and Bax, and down-regulation of Bcl-2 with L-theanine. It also corrected abnormal expressions of tumor and EMT markers. L-theanine reduced oxidative stress and inflammation by boosting CAT activity, SOD, and GSH levels, while decreasing MDA content and ROS intensity in CRC rats. It decreased pro-inflammatory cytokines IL-1β, TNF-α, and IL-6, increased anti-inflammatory IL-10, and reduced COX2, NF-κB p65, and NLRP3 protein levels. L-theanine altered the gut microbiota composition in CRC rat models, resulting in 379 new strains and reduced levels of genera like Kineothrix and Parasutterella. Immunohistochemical analysis showed increased GPR41 expression in the DMH group versus controls. These novel findings suggest L-theanine's potential as a distinct chemopreventive agent for CRC due to its beneficial and unique effects.