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Please use this identifier to cite or link to this item: http://hdl.handle.net/11375/26212
Title: Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression
Authors: Nashed MG
Ungard RG
Young K
Zacal NJ
Seidlitz EP
Fazzari J
Frey BN
Singh G
Department: Anesthesia
Keywords: Amino Acid Transport System y+;Animals;Behavior, Animal;Brain Neoplasms;Cell Line, Tumor;Cystine;Cytokines;Depression;Female;Glutamic Acid;Mice, Inbred BALB C;Neoplasms;Regression Analysis;Sulfasalazine
Publication Date: Feb-2017
Publisher: Springer Science and Business Media LLC
Abstract: Despite the lack of robust evidence of effectiveness, current treatment options for cancer-induced depression (CID) are limited to those developed for non-cancer related depression. Here, anhedonia-like and coping behaviours were assessed in female BALB/c mice inoculated with 4T1 mammary carcinoma cells. The behavioural effects of orally administered sulfasalazine (SSZ), a system xc- inhibitor, were compared with fluoxetine (FLX). FLX and SSZ prevented the development of anhedonia-like behaviour on the sucrose preference test (SPT) and passive coping behaviour on the forced swim test (FST). The SSZ metabolites 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) exerted an effect on the SPT but not on the FST. Although 5-ASA is a known anti-inflammatory agent, neither treatment with SSZ nor 5-ASA/SP prevented tumour-induced increases in serum levels of interleukin-1β (IL-1β) and IL-6, which are indicated in depressive disorders. Thus, the observed antidepressant-like effect of SSZ may primarily be attributable to the intact form of the drug, which inhibits system xc-. This study represents the first attempt at targeting cancer cells as a therapeutic strategy for CID, rather than targeting downstream effects of tumour burden on the central nervous system. In doing so, we have also begun to characterize the molecular pathways of CID.
URI: http://hdl.handle.net/11375/26212
metadata.dc.identifier.doi: 10.1038/srep41382
ISSN: 2045-2322
2045-2322
Appears in Collections:Anesthesia Publications

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