Sulfasalazine / GSH 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)


GSH, Glutathione: Click to Expand ⟱
Source:
Type:
Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.
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↓,
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↑,
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↝,
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↓,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

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↓, 10,  

Metal & Cofactor Biology ⓘ

FTH1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

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

Immune & Inflammatory Signaling ⓘ

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

OS↑, 2,   toxicity↓, 2,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: GSH, Glutathione
11 Sulfasalazine
2 Radiotherapy/Radiation
1 erastin
1 Cisplatin
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#:137  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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