School of Chemical and Biotechnology, SASTRA Deemed University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China.
Eur J Cancer Prev. 2019 Nov;28(6):472-482. doi: 10.1097/CEJ.0000000000000496.
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.
由于在临床前和临床试验中取得了有希望的结果且不良反应较少，化学预防抑制结直肠癌受到了广泛关注。本研究旨在探索对香豆酸（p-CA）在结直肠癌短期临床前模型中的化学预防作用机制。用 1,2-二甲基肼处理的大鼠补充 p-CA 后，结肠蛋白 cyclin B1、cdc2 和 mdm2 的表达下调，这些蛋白调节细胞周期；即刻早期反应基因 c-fos、c-jun 和 c-myc 的表达上调，这些基因调节细胞增殖。通过 Bax/Bcl-2 比值评估，补充 p-CA 还诱导了结肠中的细胞凋亡。免疫组化、免疫印迹和实时聚合酶链反应分析显示，p-CA 通过调节核因子红细胞 2 相关因子 2 的细胞质与核比值来改善体内解毒能力，有利于诱导细胞保护和解毒基因的表达。这些研究结果表明，p-CA 通过改善 1,2-二甲基肼处理大鼠结肠的解毒和细胞凋亡过程来抑制息肉形成。
