title: Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression.
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.
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Mina G
authors.initials: MG
authors.lastname: Nashed
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ungard
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Young
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Zacal
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Seidlitz
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fazzari
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, L8N 3K7, Canada.|Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, ON, L8P 3K7, Canada.
authors.forename: Benicio N
authors.initials: BN
authors.lastname: Frey
authors.affiliation: Department of Pathology &Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Gurmit
authors.initials: G
authors.lastname: Singh
mesh_terms: D027182:Amino Acid Transport System y+ / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001932:Brain Neoplasms / Q000556:secondary; D045744:Cell Line, Tumor; D003553:Cystine / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D012044:Regression Analysis; D012460:Sulfasalazine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D027182:Amino Acid Transport System y+; D016207:Cytokines; D018698:Glutamic Acid; D012460:Sulfasalazine; D003553:Cystine