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. 2022 Dec 24;24(1):311. doi: 10.3390/ijms24010311

Figure 1.

Figure 1

Shows the tryptophan-melatonin pathway (gold) and the factors that are required to enact this pathway (green). The tumor can release a number of factors to inhibit the tryptophan-melatonin pathway (orange), including pro-inflammatory cytokine induction of IDO and TDO, which decreases tryptophan availability. The induction of IDO/TDO in tumors leads to the production and release of kynurenine, which activates the AhR/CYP1B1, thereby metabolizing melatonin, as well as having a wide array of other effects. The direct or indirect release of glutamate or ATP will activate mGluR5 and P2Y1, which, like AhR activation, will increase the NAS/melatonin ratio. All pathway facilitating factors (green) are potential direct and indirect targets of tumors in the regulation of the tryptophan-melatonin pathway in other cells of the tumor microenvironment. Abbreviations: AANAT: aralkylamine N-acetyltransferase; AhR: aryl hydrocarbon receptor; ASMT: N-acetylserotonin O-methyltransferase; CYP: cytochrome P450; IDO: indoleamine 2,3-dioxygenase; mGluR5: metabotropic glutamate receptor 5; NAS: N-acetylserotonin; OAT: organic anion transporter; P2Y1r: purinergic receptor 2Y1; PEPT1/2: peptide transporter 1/2; TDO: tryptophan 2,3-dioxygenase; TPH: tryptophan hydroxylase.