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January 07, 2024, 14:31

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Comment on the "5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer " Qian-Yu Wang, Bin Wu Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Qian-Yu Wang, Bin Wu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China Corresponding author: Bin Wu, MD, PhD, Chief Doctor, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Road, Wangfujing, Dongcheng District, Beijing 100730, China. wubin0279@hotmail.com Funding: National High Level Hospital Clinical Research Funding，No. 2022-PUMCH-B-003 Reader Comment: We have read a recently published study entitled “5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer” written by Tian-Lei Zhao[1]. This study revealed that the 5-MTP inhibits CRC cell proliferation, induces apoptosis, and causes cell cycle arrest. Moreover, the investigation into the PI3K/Akt/FoxO3a signaling pathway sheds light on the molecular pathways influenced by 5-MTP. 5-Methoxytryptophan (5-MTP), a recently identified tryptophan metabolite, is produced by various cell types including fibroblasts, renal epithelial cells, smooth muscle cells, and vascular endothelial cells[2]. Current research primarily concentrates on elucidating the roles of 5-MTP in stabilizing endothelial function, showcasing anti-inflammatory properties, and demonstrating antioxidant effects[2, 3]. However, the scope of research on its involvement in tumorigenesis remains relatively limited. Recent investigations have shed light on the potential impact of 5-MTP in cancer contexts. One notable finding suggests that serum 5-MTP levels may play a role in influencing the prognosis of patients with hepatocellular carcinoma[4]. Additionally, intriguing insights have been gleaned from studies demonstrating that 5-MTP can enhance the sensitivity of head and neck squamous cancer cells to cisplatin[5]. This effect is attributed to the inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) [5]. This article represents the pioneering revelation that 5-MTP exhibits the potential to impede the proliferation and induce apoptosis in colorectal cancer (CRC) cells. However, it is imperative to acknowledge that there is a considerable journey ahead. First, further in vivo experiments, including animal studies, are essential to corroborate the observed effects and ascertain the translational viability of 5-MTP within a more intricate biological milieu. Second, the authors have successfully showcased the inhibitory impact of 5-MTP on apoptosis, cell cycle arrest, migration, and invasion in the HCT116 cell line. However, it remains imperative to extend this validation to other cell lines, such as HCT15 and SW480, in order to comprehensively evaluate the generalizability of these findings. Lastly, enhancing the clinical translation value of 5-MTP in colorectal cancer necessitates the exploration of relevant clinical data or the implementation of bioinformatics analyses. Investigating the correlation between 5-MTP or related genes and the prognosis of CRC patients can provide valuable insights, ultimately strengthening the potential clinical application of 5-MTP in the context of colorectal cancer. Reference: 1 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 2 Wu KK. Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite. Front Pharmacol 2021; 12: 759199 [PMID: 34858185 PMCID: Q1 DOI: 10.3389/fphar.2021.759199] 3 Wu KK, Kuo C-C, Yet S-F, Lee C-M, Liou J-Y. 5-methoxytryptophan: an arsenal against vascular injury and inflammation. J Biomed Sci 2020; 27(1): 79 [PMID: 32635910 PMCID: Q1 DOI: 10.1186/s12929-020-00671-w] 4 Ko B-S, Liang S-M, Chang T-C, Wu J-Y, Lee P-H, Hsu Y-J, Kuo C-C, Liou J-Y, Wu KK. Association of Tumor Hydroxyindole O-Methyltransferase and Serum 5-Methoxytryptophan with Long-Term Survival of Hepatocellular Carcinoma. Cancers (Basel) 2021; 13(21) [PMID: 34771474 PMCID: Q2 DOI: 10.3390/cancers13215311] 5 Su Y-C, Wang C-C, Weng J-H, Yeh S-A, Chen P-J, Hwang T-Z, Chen H-C. 5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3). Front Oncol 2022; 12: 834941 [PMID: 35936759 PMCID: Q2 DOI: 10.3389/fonc.2022.834941]

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