CoChat
Sign Up
Cited by 39Amino Acid Enzymes and MetabolismSulfur Compounds in BiologyCancer Research and Treatments

In vitro studies on the lymphoma growth-inhibitory activity of sulfasalazine

Gout, Peter W., Simms, Chris R., Robertson, May C.·2003·Anti-Cancer Drugs
DOI 10.1097/00001813-200301000-00004
Open this paper in CoChat — free account

Abstract

Sulfasalazine (SASP) is a novel, potent inhibitor of cellular cystine uptake mediated by the x(c)- cystine/glutamate antiporter. Lymphoid cells cannot synthesize cyst(e)ine and depend for growth on its uptake from their micro-environment. We previously showed that SASP (0.2 mM) can abrogate lymphoma cell proliferation in vitro by specifically inhibiting x(c)- -mediated cystine uptake. Intraperitoneal administration of SASP to Noble rats markedly suppressed Nb2-U17 rat lymphoma transplant growth, notably without major toxicity to the hosts. Since Nb2-U17 cells are x(c)- -deficient, the growth arrest was apparently not due to SASP-tumor cell interaction, but possibly to interference with x(c)- -mediated cysteine secretion by somatic cells. In this study we found that replication of x(c)- -deficient Nb2-11 lymphoma cells can be sustained in vitro, in the absence of cystine uptake enhancers, by co-culturing with IMR-90 fibroblasts known to secrete cysteine. SASP, at 0.15 and 0.2 mM, arrested replication of fibroblast-driven Nb2-11 cells by 93 and 100%, respectively, without impeding fibroblast proliferation. Addition of 2-mercapto-ethanol (60 microM), a cystine uptake enhancer, almost completely prevented this growth arrest, indicating that SASP specifically inhibited cysteine secretion by the fibroblasts, a process based on x(c)- -mediated cystine uptake. It is proposed that the lymphoma growth-inhibitory activity of SASP in vivo involves inhibition of cysteine secretion by tumor-associated somatic cells (macrophages, dendritic cells), leading to cysteine starvation of the tumor cells and apoptosis. The difference between the lymphoma cells and fibroblasts in sensitivity to SASP treatment is consistent with the marked antitumor effect of SASP lacking significant side effects.

Integrity signals

Registry

Crossref · 10.1097/00001813-200301000-00004

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Sulfasalazine potently inhibited growth of lymphomas with low-level expression of SLC7A11, a subunit of system xc−.

    “sulfasalazine potently inhibited the growth of lymphomas with low-level expression of SLC7A11, a subunit of system xc− [77, 78].”

    From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [78]

  • DLBCLs with low system xc− activity are more susceptible to ferroptosis.

    “DLBCLs with low system xc− activity are more susceptible to ferroptosis”

    From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [78]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Gout, P. W., Simms, C. R., & Robertson, M. C.
Affiliations
BC Cancer Agency (CA)
Corresponding author
Gout, Peter W.
Venue
Anti-Cancer Drugs
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2003-01
Volume
14
Issue
1
Pages
21-29
ISSN
0959-4973 (ISSN-L)
DOI
10.1097/00001813-200301000-00004
OpenAlex
W2333517888
Cited by
39
References
30
Citations by year
2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 3
FWCI
0.47
Type
journal article
Language
en
Open access
closed
Locations
  • Anti-Cancer Drugs (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
Keywords
sulfasalazine, lymphoma, cystine uptake, tumor growth inhibition, IMR-90 fibroblasts, 2-mercaptoethanol, apoptosis, tumor-associated macrophages, anticancer activity
MeSH terms
Animals, Cells, Cultured, Growth Inhibitors, Humans, Lymphoma, Male, Sulfasalazine, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review