5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis

5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis

Cyclooxygenase-2(COX-2) overexpression promotes inflammation and tumorigenesis. COX-2 expression in response to diverse stimuli is tightly controlled to avoid persistent overexpression. 5-methoxyindole metabolites of L-tryptophan represent a new class of compounds that control COX-2 expression at th...

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Main Authors: Wu, Kenneth K, Cheng, Huei-Hsuan, Chang, Tzu-Ching
Format: Online
Language:English
Published: BioMed Central 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975872/
id pubmed-3975872
recordtype oai_dc
spelling pubmed-39758722014-04-05 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis Wu, Kenneth K Cheng, Huei-Hsuan Chang, Tzu-Ching Review Cyclooxygenase-2(COX-2) overexpression promotes inflammation and tumorigenesis. COX-2 expression in response to diverse stimuli is tightly controlled to avoid persistent overexpression. 5-methoxyindole metabolites of L-tryptophan represent a new class of compounds that control COX-2 expression at the transcriptional level. Two of the metabolites, the newly discovered 5-methoxytryptophan (5-MTP, also known as cytoguardin) and N-acetyl 5-methoxytryptamine (melatonin) are the focus of this review. 5-MTP is produced by mesenchymal cells such as fibroblasts via 5-hydroxytryptophan (5-HTP). It inhibits COX-2 transcriptional activation induced by diverse proinflammatory and mitogenic factors. Cancer cells are deficient in cytoguardin production which contributes to COX-2 overexpression. Fibroblast-generated 5-MTP is capable of restoring the control of COX-2 overexpression in cancer cells. 5-MTP blocks cancer cell migration and invasion in vitro and inhibits tumor growth and cancer metastasis in a xenograft model. Melatonin possesses similar COX-2 suppressing and anti-cancer properties albeit at supra-pharmacological concentrations. By contrast, 5-hydroxyindole metabolites of L-tryptophan such as 5-hydroxytryptamine (serotonin), 5-hydroxytryptophol and other serotonin catabolites do not control COX-2 expression. 5-hydroxytryptophan inhibits COX-2 expression through conversion to 5-MTP. The physiological relevance of 5-MTP as an endogenous regulator of inflammation and cancer metastasis remains to be investigated. On the other hand, 5-methoxyindole metabolites of tryptophan are valuable lead compounds for development of new anti-inflammatory drugs and cancer chemoprevention. BioMed Central 2014-03-03 /pmc/articles/PMC3975872/ /pubmed/24589238 http://dx.doi.org/10.1186/1423-0127-21-17 Text en Copyright © 2014 Wu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Wu, Kenneth K
Cheng, Huei-Hsuan
Chang, Tzu-Ching
spellingShingle Wu, Kenneth K
Cheng, Huei-Hsuan
Chang, Tzu-Ching
5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
author_facet Wu, Kenneth K
Cheng, Huei-Hsuan
Chang, Tzu-Ching
author_sort Wu, Kenneth K
title 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
title_short 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
title_full 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
title_fullStr 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
title_full_unstemmed 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis
title_sort 5-methoxyindole metabolites of l-tryptophan: control of cox-2 expression, inflammation and tumorigenesis
description Cyclooxygenase-2(COX-2) overexpression promotes inflammation and tumorigenesis. COX-2 expression in response to diverse stimuli is tightly controlled to avoid persistent overexpression. 5-methoxyindole metabolites of L-tryptophan represent a new class of compounds that control COX-2 expression at the transcriptional level. Two of the metabolites, the newly discovered 5-methoxytryptophan (5-MTP, also known as cytoguardin) and N-acetyl 5-methoxytryptamine (melatonin) are the focus of this review. 5-MTP is produced by mesenchymal cells such as fibroblasts via 5-hydroxytryptophan (5-HTP). It inhibits COX-2 transcriptional activation induced by diverse proinflammatory and mitogenic factors. Cancer cells are deficient in cytoguardin production which contributes to COX-2 overexpression. Fibroblast-generated 5-MTP is capable of restoring the control of COX-2 overexpression in cancer cells. 5-MTP blocks cancer cell migration and invasion in vitro and inhibits tumor growth and cancer metastasis in a xenograft model. Melatonin possesses similar COX-2 suppressing and anti-cancer properties albeit at supra-pharmacological concentrations. By contrast, 5-hydroxyindole metabolites of L-tryptophan such as 5-hydroxytryptamine (serotonin), 5-hydroxytryptophol and other serotonin catabolites do not control COX-2 expression. 5-hydroxytryptophan inhibits COX-2 expression through conversion to 5-MTP. The physiological relevance of 5-MTP as an endogenous regulator of inflammation and cancer metastasis remains to be investigated. On the other hand, 5-methoxyindole metabolites of tryptophan are valuable lead compounds for development of new anti-inflammatory drugs and cancer chemoprevention.
publisher BioMed Central
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975872/
_version_ 1612074240821952512

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