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

World J Gastroenterol. 2023 Dec 21;29(47):6148-6160. doi: 10.3748/wjg.v29.i47.6148.

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

MeSH terms

  • Animals
  • Apoptosis
  • Colorectal Neoplasms* / drug therapy
  • HCT116 Cells
  • Humans
  • Phosphatidylinositol 3-Kinases*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • Tryptophan / pharmacology

Substances

  • 5-methoxytryptophan
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Tryptophan