5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer

doi:10.3748/wjg.v29.i47.6148

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World Journal of Gastroenterology

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1007-9327

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Basic Study

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.

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.