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 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. © 2014 wu et al.; licensee biomed central ltd.