Database Query Results : Sulfasalazine, ,

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)


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↓,
5141- SAS,    Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B
- in-vitro, CRC, SW-620
NF-kB↓,
5140- SAS,    Suppression of NF-κB activity by sulfasalazine is mediated by direct inhibition of IκB kinases α and β
- in-vitro, AML, Jurkat - in-vitro, CRC, SW-620
TNF-α↓, IKKα↓, NF-kB↓,
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↓,
5138- SAS,  Rad,    Drug repurposing: sulfasalazine sensitizes gliomas to gamma knife radiosurgery by blocking cystine uptake through system Xc-, leading to glutathione depletion
- vitro+vivo, GBM, NA
cystine↓, GSH↓, ROS↑, RadioS↑, eff↓, DNAdam↑, OS↑,
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↓,
3853- SAS,    Sulfur-containing therapeutics in the treatment of Alzheimer's disease
- Review, AD, NA
*antiOx↑,
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↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

cystine↓, 1,   Ferroptosis↑, 4,   GPx4↓, 1,   GSH↓, 11,   H2O2↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 8,   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 ⓘ

DNAdam↑, 1,   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 ⓘ

IKKα↓, 1,   IL1↓, 1,   IL2↓, 1,   Inflam↓, 2,   NF-kB↓, 3,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↓, 3,   eff↑, 2,   RadioS↓, 1,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

BMPs↑, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

Mood↑, 1,   OS↑, 3,   toxicity↓, 3,  
Total Targets: 49

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   xCT↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Functional Outcomes ⓘ

toxicity↝, 1,  
Total Targets: 4

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#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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