Zhao TL, Qi Y, Wang YF, Wang Y, Liang H, Pu YB. 5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer. World J Gastroenterol 2023; 29(47): 6148-6160 [PMID: 38186686 DOI: 10.3748/wjg.v29.i47.6148]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
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
ARTICLE HIGHLIGHTS
Research background
Colorectal cancer (CRC) is a highly prevalent malignant tumor. Research is needed to find and develop effective drugs for the treatment of CRC. 5-methoxytryptophan (5-MTP) is a tryptophan metabolite found in animals and humans. The effect of 5-MTP on the proliferation and apoptosis of CRC cells is still unclear.
Research motivation
Our work explored the effects of 5-MTP on the proliferation, migration, invasion and apoptosis of CRC cells. We tried to explore the potential of 5-MTP as a drug for the treatment of CRC.
Research objectives
Here, we studied that 5-MTP combined with PI3K/Akt/FOXO3a signaling pathway inhibitor can significantly promote apoptosis and cell cycle arrest of CRC cells, and inhibit cell proliferation. 5-MTP can be used as an effective drug in the treatment of CRC.
Research methods
In this study, a series of experiments were carried out. Colony forming assay and Cell Counting Kit were used to detect the effect of 5-MTP on the proliferation of CRC cell lines. The effect of 5-MTP on cell growth was detected by cell cycle analysis. In addition, the effects of 5-MTP on apoptosis and reactive oxygen species of HCT-116 cells were studied. In order to further explore the effect of 5-MTP on CRC, we studied the effect of 5-MTP on PI3K/Akt signaling pathway in CRC cells.
Research results
5-MTP can promote apoptosis and cell cycle arrest of CRC cells, and inhibit cell proliferation. However, compared with 5-MTP alone, 5-MTP combined with PI3K/Akt/FOXO3a signaling pathway inhibitors significantly promoted apoptosis and cell cycle arrest of CRC cells, and inhibited cell proliferation. It provides new insights into the mechanism of drug action.
Research conclusions
5-MTP combined with PI3K/Akt/FOXO3a signaling pathway inhibitor significantly promoted apoptosis and cell cycle arrest of CRC cells, and inhibited cell proliferation.
Research perspectives
This study confirmed that 5-MTP combined with PI3K/Akt/FOXO3a signaling pathway inhibitor could significantly promote the apoptosis and cell cycle arrest of CRC cells, and inhibit cell proliferation. These results provide a new direction for the drug treatment of CRC. However, the study of mechanism in this study is relatively limited. Therefore, further analysis, nude mouse experiments and more cell experiments are needed to explore its mechanism.
