Tryptophan catabolites along the indoleamine 2,3-dioxygenase pathway as a biological link between depression and cancer.

Abstract:

:Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway, is induced by interferon-γ, interleukin-6, TNF-α, and oxidative stress. IDO catabolizes tryptophan, the amino acid precursor of serotonin and melatonin, to the metabolites collectively called TRYCATs. TRYCAT pathway activation is accompanied by downregulation of immune cell proliferation, function, and survival. The increase in IDO activity in tumor microenvironments is related to tumor cell escape from immune surveillance. Despite the evidence of inflammatory mechanisms underlying cancer and depression, it is important to emphasize that both diseases are heterogeneous and, as such, inflammatory mechanisms may not be relevant to all patients. Thus, the purpose of this review is to examine whether detrimental TRYCATs - synthesis of which increases in depression and cancer - are a pathophysiological link between the two diseases, and whether IDO is a potential pharmacological target for the treatment of the comorbid depression and cancer.

journal_name

Behav Pharmacol

journal_title

Behavioural pharmacology

authors

Barreto FS,Chaves Filho AJM,de Araújo MCCR,de Moraes MO,de Moraes MEA,Maes M,de Lucena DF,Macedo DS

doi

10.1097/FBP.0000000000000384

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

165-180

issue

2 and 3-Spec Issue

eissn

0955-8810

issn

1473-5849

pii

00008877-201804000-00007

journal_volume

29

pub_type

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