Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2023; 29(47): 6148-6160
Published online Dec 21, 2023. doi: 10.3748/wjg.v29.i47.6148
5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer
Tian-Lei Zhao, Yue Qi, Yi-Fan Wang, Yi Wang, Hui Liang, Ya-Bin Pu
Tian-Lei Zhao, Yue Qi, Yi-Fan Wang, Yi Wang, Ya-Bin Pu, Department of General Surgery, Naval Medical Center of PLA, Shanghai 200052, China
Hui Liang, Department of Gastroenterology, Naval Medical Center of PLA, Shanghai 200052, China
Co-first authors: Tian-Lei Zhao and Yue Qi.
Co-corresponding authors: Hui Liang and Ya-Bin Pu.
Author contributions: Pu YB and Liang H conceived and designed the study; Zhao TL and Qi Y performed the experiments and prepared the manuscript, they made the same contribution to this work and should share the first authorship; Wang YF and Wang Y analyzed the data; Pu YB and Liang H conceived, designed this study, and revised the manuscript; Pu YB and Liang H have the same contribution to this work, they should be listed as co-corresponding authors; and all authors have read and approved the final version of the manuscript.
Institutional review board statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by Institutional Review Board of Naval Medical Center of PLA.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ya-Bin Pu, MMed, Associate Chief Physician, Department of General Surgery, Naval Medical Center of PLA, No. 338 Huaihai Road, Changning District, Shanghai 200052, China. yabinpu26@163.com
Received: September 6, 2023
Peer-review started: September 6, 2023
First decision: November 1, 2023
Revised: November 4, 2023
Accepted: December 4, 2023
Article in press: December 4, 2023
Published online: December 21, 2023
Processing time: 103 Days and 18.1 Hours
Abstract
BACKGROUND

Colorectal cancer (CRC) is a highly prevalent malignancy worldwide, and new therapeutic targets urgently need to be found to prolong patient survival. 5-methoxytryptophan (5-MTP) is a tryptophan metabolite found in animals and humans. However, the effects of 5-MTP on proliferation and apoptosis of CRC cells are currently unknown.

AIM

To investigate the effects of 5-MTP on the proliferation, migration, invasion, and apoptosis abilities of CRC cells. Additionally, we seek to explore whether 5-MTP has the potential to be utilized as a drug for the treatment of CRC.

METHODS

In order to evaluate the effect of 5-MTP on CRC cells, a series of experiments were conducted for evaluation. Colony formation assay and Cell Counting Kit 8 assays were used to investigate the impact of 5-MTP on the proliferation of CRC cell lines. Cell cycle assays were employed to examine the effect of 5-MTP on cellular growth. In addition, we investigated the effects of 5-MTP on apoptosis and reactive oxygen species in HCT-116 cells. To obtain a deeper understanding of how 5-MTP affects CRC, we conducted a study to examine its influence on the PI3K/Akt signaling pathway in CRC cells.

RESULTS

This article showed that 5-MTP promoted apoptosis and cell cycle arrest and inhibited cell proliferation in CRC cells. In many articles, it has been reported that PI3K/Akt/FoxO3a signaling pathway is one of the most important signaling pathways involved in internal regulating cell proliferation and differentiation. Nevertheless, 5-MTP combined with PI3K/Akt/FoxO3a signaling pathway inhibitors significantly promoted apoptosis and cell cycle arrest and inhibited cell proliferation in CRC cells compared with 5-MTP alone in our study.

CONCLUSION

Therefore, there is strong evidence that 5-MTP can be used as an effective medicine for CRC treatment.

Keywords: Colorectal cancer; 5-methoxytryptophan; Apoptosis; Cell cycle arrest; PI3K/Akt signaling pathway

Core Tip: Colorectal cancer (CRC) is insensitive to radiotherapy and has poor therapeutic efficacy, and there is an urgent need to find new therapeutic targets to prolong patient survival. 5-methoxytryptophan (5-MTP) is a tryptophan metabolite present in both animals and humans. 5-MTP has a wide range of physiological functions such as stabilizing endothelial function, anti-inflammation, and antioxidant to prevent cellular damage. Our study found that 5-MTP combined with an inhibitor of the PI3K/Akt/FoxO3a signaling pathway significantly promoted apoptosis and cell cycle arrest and inhibited cell proliferation in CRC cells compared with 5-MTP alone.