Tryptophan Metabolism and Cancer Progression

Authors

  • Kenneth K. Wu Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan and Institute of Biotechnology, National Tsing-Hua University, Hsinchu, Taiwan

DOI:

https://doi.org/10.30683/1927-7229.2021.10.01

Keywords:

Tryptophan metabolites, cancer progression, melatonin, 5-methoxytryptophan, kynurenine.

Abstract

Abstract: Intracellular tryptophan (Trp) is catabolized to a large repertoire of metabolites via two major pathways: indoleamine and tryptophan 2, 3-dioxygenases (IDO/TDO) and Trp hydroxylase (TPH) pathways. The catabolites possess diverse biological activities and carry out various physiological functions. Several catabolites such as kynurenine (Kyn) and serotonin promote while melatonin and 5-methoxytryptophan (5-MTP) suppress cancer growth and metastasis. Cancer cell-derived Kyn enhances cancer growth and evasion of immunosurveillance by interacting with cancer cell and immune cell membrane aryl hydrocarbon receptors (AHR), respectively. Serotonin exerts its tumor-promoting activities through type 1 and type 2 serotonin receptors. 5-MTP and melatonin suppress cancer growth and metastasis by common mechanisms, i.e., inhibition of p300 histone acetyltransferase (HAT) and NF-κB activation, and suppression of cyclooxygenase-2 and cytokine transcription. Both metabolites block p38 MAPK signaling pathway. Human cancer tissues express increased levels of IDO, TDO and kynurenine monooxygenase (KMO) which are correlated with reduced patient survival. In summary, cancer Trp metabolism regulates cancer growth and metastasis by complex mechanisms. 5-MTP and melatonin provide valuable lead to develop new drugs for chemo-prevention and adjuvant therapy of cancer.

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Published

2021-09-16 — Updated on 2021-09-16

How to Cite

K. Wu, K. (2021). Tryptophan Metabolism and Cancer Progression . Journal of Analytical Oncology, 10(1), 1–11. https://doi.org/10.30683/1927-7229.2021.10.01

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