Supplementation of p-coumaric acid exhibits chemopreventive effect via induction of Nrf2 in a short-term preclinical model of colon cancer.
Eur J Cancer Prev. 2019 Nov ;28(6):472-482. PMID: 30407216
Sharada H Sharma
Suppression of colorectal cancer by means of chemoprevention is gaining great attention owing to promising outcomes with less adverse effects in preclinical and clinical trials. The present study aims to explore the mechanism of chemoprevention by p-coumaric acid (p-CA) in a short-term preclinical model of colon cancer. 1,2-dimethylhydrazine-administered rats supplemented with p-CA showed downregulation of the expression of colonic proteins, namely, cyclin B1, cdc2 and mdm2, which regulate cell cycle, and immediate early response genes, namely, c-fos, c-jun and c-myc, which regulate cell proliferation. Apoptosis induction was also observed in the colon of p-CA-supplemented rats as assessed by the Bax/Bcl-2 ratio. Immunohistochemistry, immunoblotting and real-time polymerase chain reaction analysis revealed that supplementation of p-CA improved the in-vivo detoxification potential by modulating the cytoplasmic-to-nuclear ratio of nuclear factor erythroid 2-related factor 2, favouring the induction of genes responsible for cytoprotection and detoxification. The outcome of these findings suggests that p-CA inhibited polyp formation by improving the process of detoxification and apoptosis in the colon of 1,2-dimethylhydrazine-administered rats.