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Tryptophan catabolites along the indoleamine 2,3-dioxygenase pathway as a biological link between depression and cancer
- Source :
- Behavioural pharmacology. 29(2 and)
- Publication Year :
- 2018
-
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.
- Subjects :
- 0301 basic medicine
Serotonin
Indoles
Inflammation
Major histocompatibility complex
03 medical and health sciences
Immune system
Downregulation and upregulation
Neoplasms
medicine
Animals
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
Indoleamine 2,3-dioxygenase
Pharmacology
Tumor microenvironment
Depressive Disorder
biology
business.industry
Depression
Immunity
Tryptophan
Cancer
medicine.disease
Psychiatry and Mental health
Oxidative Stress
030104 developmental biology
biology.protein
Cancer research
medicine.symptom
business
Signal Transduction
Subjects
Details
- ISSN :
- 14735849
- Volume :
- 29
- Issue :
- 2 and
- Database :
- OpenAIRE
- Journal :
- Behavioural pharmacology
- Accession number :
- edsair.doi.dedup.....ad37893f2dc7b4c089d70dc24a041a62