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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2020; 12(2): 149-172
Published online Feb 15, 2020. doi: 10.4251/wjgo.v12.i2.149
Caffeine and its main targets of colorectal cancer
Wen-Qi Cui, Shi-Tong Wang, Dan Pan, Bing Chang, Li-Xuan Sang
Wen-Qi Cui, Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Wen-Qi Cui, Shi-Tong Wang, China Medical University 101K class 87, Shenyang 110001, Liaoning Province, China
Shi-Tong Wang, Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Dan Pan, Li-Xuan Sang, Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Bing Chang, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Sang LX designed the study; Cui WQ wrote the original draft; Cui WQ, Wang ST, Pan D, Chang B and Sang LX reviewed and edited; All authors read, revised and approved the final manuscript.
Supported by the innovative talents support program of institution of higher learning of Liao Ning province, No. 2018-478; The innovative talents of science and technology support program of young and middle-aged people of Shenyang, No. RC170446.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Li-Xuan Sang, PhD, Doctor, Department of Geriatrics, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, China. sanglixuan2008@163.com
Received: September 12, 2019
Peer-review started: September 12, 2019
First decision: October 14, 2019
Revised: October 25, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: February 15, 2020
Processing time: 155 Days and 23.2 Hours
Abstract

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 Escherichia coli and Candida albicans 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.

Keywords: Caffeine; Colorectal cancer; Epidemiology; Signaling pathway; Immune response; Cell cycle

Core tip: Increasing evidence indicates that caffeine has wide-ranging effects on pathogenesis, metastasis and prognosis of colorectal cancer. This study systematically reviewed the literature on the targets and effects of caffeine on colorectal cancer. The effects were categorized into five groups: (1) communicating with cell signaling; (2) modulating immune response; (3) influencing gut bacteria; (4) regulating cell cycle; and (5) redox homeostasis.