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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2018; 6(13): 577-588
Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.577
Role of bile acids in colon carcinogenesis
Thi Thinh Nguyen, Trong Thuan Ung, Nam Ho Kim, Young Do Jung
Thi Thinh Nguyen, Trong Thuan Ung, Young Do Jung, Department of Biochemistry, Chonnam National University Medical School, Jeonnam 58138, South Korea
Nam Ho Kim, Department of Nephrology, Chonnam National University Medical School, Gwangju 501-190, South Korea
Author contributions: Nguyen TT and Ung TT performed the data collection and wrote the paper; Kim NH and Jung YD reviewed and edited the paper.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Young Do Jung, MD, PhD, Professor, Department of Biochemistry, Chonnam National University Medical School, Seoyang Ro 264, Hwasun, Jeonnam 58138, South Korea. ydjung@chonnam.ac.kr
Telephone: +82-61-3792772 Fax: +82-61-3792781
Received: June 20, 2018
Peer-review started: June 20, 2018
First decision: August 29, 2018
Revised: September 15, 2018
Accepted: October 11, 2018
Article in press: October 12, 2018
Published online: November 6, 2018
Processing time: 139 Days and 8.3 Hours
Abstract

Bile acids (BAs) are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption. There are numerous scientific reports describing BAs, especially secondary BAs, as strong carcinogens or promoters of colon cancers. Firstly, BAs act as strong stimulators of colorectal cancer (CRC) initiation by damaging colonic epithelial cells, and inducing reactive oxygen species production, genomic destabilization, apoptosis resistance, and cancer stem cells-like formation. Consequently, BAs promote CRC progression via multiple mechanisms, including inhibiting apoptosis, enhancing cancer cell proliferation, invasion, and angiogenesis. There are diverse signals involved in the carcinogenesis mechanism of BAs, with a major role of epidermal growth factor receptor, and its down-stream signaling, involving mitogen-activated protein kinase, phosphoinositide 3-kinase/Akt, and nuclear factor kappa-light-chain-enhancer of activated B cells. BAs regulate numerous genes including the human leukocyte antigen class I gene, p53, matrix metalloprotease, urokinase plasminogen activator receptor, Cyclin D1, cyclooxygenase-2, interleukin-8, and miRNAs of CRC cells, leading to CRC promotion. These evidence suggests that targeting BAs is an efficacious strategies for CRC prevention and treatment.

Keywords: Apoptosis resistance; Cancer stemness; Bile acids; Colorectal cancer; Reactive oxygen species; Angiogenesis

Core tip: Even though there is a close relationship between a high concentration of bile acids (BAs) and high risk of colorectal cancer (CRC), the mechanism of BAs promoting colon carcinogenesis is still not fully understood. In this review paper, we discuss molecular mechanisms of BAs as CRC promoters, their role in CRC progression, the oncogenic genes and signaling pathways involved, and important therapies against BA-related CRC.