Cui Wen-Qi, Wang Shi-Tong, Pan Dan, Chang Bing, Sang Li-Xuan
Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
World J Gastrointest Oncol. 2020 Feb 15;12(2):149-172. doi: 10.4251/wjgo.v12.i2.149.
Caffeine is a purine alkaloid and is widely consumed in coffee, soda, tea, chocolate and energy drinks. To date, a growing number of studies have indicated that caffeine is associated with many diseases including colorectal cancer. Caffeine exerts its biological activity through binding to adenosine receptors, inhibiting phosphodiesterases, sensitizing calcium channels, antagonizing gamma-aminobutyric acid receptors and stimulating adrenal hormones. Some studies have indicated that caffeine can interact with signaling pathways such as transforming growth factor β, phosphoinositide-3-kinase/AKT/mammalian target of rapamycin and mitogen-activated protein kinase pathways through which caffeine can play an important role in colorectal cancer pathogenesis, metastasis and prognosis. Moreover, caffeine can act as a general antioxidant that protects cells from oxidative stress and also as a regulatory factor of the cell cycle that modulates the DNA repair system. Additionally, as for intestinal homeostasis, through the interaction with receptors and cytokines, caffeine can modulate the immune system mediating its effects on T lymphocytes, B lymphocytes, natural killer cells and macrophages. Furthermore, caffeine can not only directly inhibit species in the gut microbiome, such as and but also can indirectly exert inhibition by increasing the effects of other antimicrobial drugs. This review summarizes the association between colorectal cancer and caffeine that is being currently studied.
咖啡因是一种嘌呤生物碱，广泛存在于咖啡、汽水、茶、巧克力和能量饮料中。迄今为止，越来越多的研究表明，咖啡因与包括结直肠癌在内的多种疾病有关。咖啡因通过与腺苷受体结合、抑制磷酸二酯酶、使钙通道敏感、拮抗γ-氨基丁酸受体以及刺激肾上腺激素来发挥其生物活性。一些研究表明，咖啡因可与转化生长因子β、磷酸肌醇-3-激酶/蛋白激酶B/雷帕霉素靶蛋白以及丝裂原活化蛋白激酶等信号通路相互作用，通过这些通路，咖啡因在结直肠癌的发病机制、转移和预后中发挥重要作用。此外，咖啡因可作为一种通用抗氧化剂，保护细胞免受氧化应激，还可作为细胞周期的调节因子，调节DNA修复系统。另外，关于肠道内环境稳定，通过与受体和细胞因子相互作用，咖啡因可调节免疫系统，介导其对T淋巴细胞、B淋巴细胞、自然杀伤细胞和巨噬细胞的作用。此外，咖啡因不仅可直接抑制肠道微生物群中的物种，如 和 ，还可通过增强其他抗菌药物的作用间接发挥抑制作用。本综述总结了目前正在研究的结直肠癌与咖啡因之间的关联。
