Sulfasalazine / xCT Cancer Research Results

SAS, Sulfasalazine: Click to Expand ⟱
Features:
Sulfasalazine is primarily known as an anti-inflammatory and disease‐modifying antirheumatic drug (DMARD), used for conditions such as rheumatoid arthritis and inflammatory bowel diseases (e.g., ulcerative colitis).

-Inhibit the nuclear factor kappa B (NF-κB) pathway.
-Sulfasalazine has been noted to interfere with the cystine/glutamate antiporter (system x_c⁻), which can reduce glutathione levels in cancer cells, potentially making them more susceptible to oxidative stress.

-Ability to inhibit anti-oxidant production (for ProOxidant effect).

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 System xC− (xCT/SLC7A11 cystine–glutamate antiporter) ↓ cystine uptake Limits cystine supply Sulfasalazine is used as an xCT inhibitor; blocking cystine uptake is the core upstream action in cancer models (ref)
2 Glutathione biosynthesis / GSH pool ↓ GSH Loss of redox buffering In glioma cells, cystine uptake blockade by sulfasalazine leads to glutathione depletion (ref)
3 ROS accumulation ↑ ROS Oxidative stress amplification Glioma study: sulfasalazine increases ROS after GSH depletion (mechanistic sequence shown) (ref)
4 DNA damage (oxidative/genotoxic stress) ↑ DNA damage Checkpoint/death signaling Glioma study: sulfasalazine causes DNA damage as part of the ROS-driven cytotoxic cascade (ref)
5 Radiosensitization (oxidative vulnerability) ↑ radiation sensitivity Enhances radiotherapy effect Melanoma model: sulfasalazine decreases glutathione and synergistically enhances X-irradiation cytotoxicity (ref)
6 Ferroptosis (system xC− → GSH/GPX4 vulnerability) ↑ ferroptotic death Iron-dependent oxidative death Paclitaxel-resistant uterine serous carcinoma model: sulfasalazine (xCT inhibitor) induces ferroptotic cell death signatures (ref)
7 Mitochondrial apoptosis (caspase pathway) ↑ apoptosis Programmed cell death Osteosarcoma work: sulfasalazine blocks system xC− and induces cell death consistent with ferroptosis/apoptosis programs (apoptosis markers reported in the paper’s mechanism set) (ref)
8 NF-κB activation (IκBα degradation / IKK activity) ↓ NF-κB activation Reduced pro-survival/inflammatory transcription Mechanistic paper shows sulfasalazine blocks NF-κB activation by inhibiting IκBα degradation via IKK inhibition (ref)
9 NF-κB nuclear translocation ↓ nuclear NF-κB Transcriptional shutdown Colon cancer cells: sulfasalazine prevents TNFα-induced NF-κB nuclear translocation and NF-κB–dependent transcription (ref)
10 Chemo-sensitization via xCT inhibition ↑ chemo sensitivity (context-dependent) Combination benefit Mechanistic rationale: xCT inhibition lowers GSH and oxidative defense, increasing sensitivity to cytotoxic stress (glioma + radiation shown explicitly) (ref)
11 Tumor growth suppression in vivo (xCT-targeted stress) ↓ tumor growth Anti-tumor efficacy Glioma xenograft model: sulfasalazine plus radiosurgery improves survival compared to control/monotherapy (ref)
12 Resistance axis: xCT-high / antioxidant-high tumors ↑ vulnerability when xCT-high Targeted susceptibility Endometrial/USC model: sulfasalazine shows stronger cytotoxicity in resistant (stress-adapted) cells consistent with xCT dependence (ref)


xCT, SLC7A11: Click to Expand ⟱
Source:
Type: protein
SLC7A11 (also known as xCT) xenobiotic transporter.
XCT (xenobiotic transporter) is a protein that plays a crucial role in the transport of xenobiotics, including chemotherapeutic agents, across cell membranes.
xCT overexpressed in: breast, lung, colon, prostate, GBM, Pancreatic (with poor prognosis) Cancer cells often experience high levels of oxidative stress; upregulation of SLC7A11 helps to counteract this stress and supports cell survival.

Targeting SLC7A11 can sensitize tumor cells to oxidative damage and ferroptosis, offering a potential therapeutic avenue.

SLC7A11 encodes the light chain subunit of the cystine/glutamate antiporter system X_c⁻. This transporter imports cystine into the cell and exports glutamate out. The imported cystine is then used to synthesize glutathione (GSH), a major antioxidant that helps control intracellular ROS levels.

Many cancer cells experience elevated oxidative stress due to increased metabolic activity and stress conditions within the tumor microenvironment. Upregulation of SLC7A11 can provide a survival advantage by boosting GSH synthesis, thereby neutralizing ROS and preventing oxidative damage.

High SLC7A11 activity helps prevent ferroptosis by ensuring continuous glutathione production. Glutathione is a cofactor for glutathione peroxidase 4 (GPX4), a key enzyme that detoxifies lipid peroxides.
Mechanism: When SLC7A11 is inhibited, cystine uptake is reduced. This leads to glutathione depletion, compromised GPX4 activity, and eventually the accumulation of lipid peroxides that trigger ferroptosis.
Inducing ferroptosis has become a promising anticancer strategy. Inhibitors targeting SLC7A11 (or related pathways) can lower glutathione levels, increasing susceptibility to ferroptotic cell death. This is especially attractive in cancers with high SLC7A11 expression, where blocking its function may selectively induce ferroptosis and overcome drug resistance.
Scientific Papers found: Click to Expand⟱
5046- erastin,  SAS,    The structure of erastin-bound xCT–4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis
- Study, Var, NA
xCT↓, ROS↑, TumCG↓, GSH↓, Ferroptosis↑,
5042- SAS,    xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling
- Review, Var, NA
xCT↓, GSH↓, TumCG↓, TumCI↓, ROS↑, RadioS↑, eff↓,
5139- SAS,    Sulfasalazine induces ferroptosis in osteosarcomas by regulating Nrf2/SLC7A11/GPX4 signaling axis
- in-vitro, OS, MG63 - in-vitro, OS, U2OS
*Inflam↓, TumCP↓, TumCMig↓, Apoptosis↑, Ferroptosis↑, Iron↑, MDA↑, ROS↑, GSH↓, SOD↓, MMP↓, NRF2↓, xCT↓, GPx4↓, FTH1↓,
5045- SAS,    Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells
- in-vivo, Var, NA
xCT↓, GSH↓, BMPs↑, Diff↑,
5044- SAS,    xCT inhibitor sulfasalazine depletes paclitaxel-resistant tumor cells through ferroptosis in uterine serous carcinoma
- in-vitro, Var, NA
xCT↓, Ferroptosis↑, ROS↑, IL1↓, IL2↓, NF-kB↓, GSH↓, TumCG↓, ChemoSen↑,
5043- SAS,    Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects
- in-vivo, Nor, NA
*toxicity↝, *xCT↓, toxicity↓,
5041- SAS,  Cisplatin,    Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism
- in-vitro, CRC, NA
xCT↓, Inflam↓, Apoptosis↓, GSH↓, ROS↑, TumCG↓, selectivity↑, eff↑, eff↓,
5040- SAS,    Structure-Activity-Relationship-Aided Design and Synthesis of xCT Antiporter Inhibitors
- in-vitro, GBM, A172 - in-vitro, Melanoma, A375 - in-vitro, GBM, U87MG - in-vitro, BC, MCF-7
GSH↓, toxicity↓, xCT↓,
5039- SAS,    Regulatory network of ferroptosis and autophagy by targeting oxidative stress defense using sulfasalazine in triple-negative breast cancer
- vitro+vivo, BC, NA
xCT↓, ROS↑, GSH↓, Ferroptosis↑, TumCG↓, toxicity↓, lipid-P↑,
5038- SAS,  Rad,    Sulfasalazine, an inhibitor of the cystine-glutamate antiporter, reduces DNA damage repair and enhances radiosensitivity in murine B16F10 melanoma
- in-vivo, Melanoma, B16-F10
xCT↓, ROS↑, RadioS↓, GSH↓, selectivity↑, DNArepair↓, TumCCA↑, H2O2↑, Dose↝,
5037- SAS,    Inhibition of xCT by sulfasalazine alleviates the depression-like behavior of adult male mice subjected to maternal separation stress
- in-vivo, Nor, NA
xCT↓, Mood↑, Inflam↓, glut↓,
5036- SAS,    Targeting xCT with sulfasalazine suppresses triple-negative breast cancer growth via inducing autophagy and coordinating cell cycle and proliferation
- vitro+vivo, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
xCT↓, GSH↓, OS↑, Myc↓, CDK1↓, CD44↓, eff↑, TumCG↓,
5035- SAS,    Sulfasalazine, a potent suppressor of gastric cancer proliferation and metastasis by inhibition of xCT: Conventional drug in new use
- Human, GC, NA - in-vitro, GC, NCI-N87 - in-vitro, GC, SGC-7901
other?, TumCP↓, TumMeta↓, TumCI↓, xCT↓, OS↑,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 4,   GPx4↓, 1,   GSH↓, 10,   H2O2↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 7,   SOD↓, 1,   xCT↓, 12,  

Metal & Cofactor Biology ⓘ

FTH1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

glut↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   Apoptosis↑, 1,   Ferroptosis↑, 4,   Myc↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,  

DNA Damage & Repair ⓘ

DNArepair↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 1,   Diff↑, 1,   TumCG↓, 6,  

Migration ⓘ

TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1↓, 1,   IL2↓, 1,   Inflam↓, 2,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↓, 2,   eff↑, 2,   RadioS↓, 1,   RadioS↑, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

BMPs↑, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

Mood↑, 1,   OS↑, 2,   toxicity↓, 3,  
Total Targets: 45

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

xCT↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Functional Outcomes ⓘ

toxicity↝, 1,  
Total Targets: 3

Scientific Paper Hit Count for: xCT, SLC7A11
13 Sulfasalazine
1 erastin
1 Cisplatin
1 Radiotherapy/Radiation
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:286  Target#:801  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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