Database Query Results : , , xCT

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⟱
1349- And,    Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction
- in-vitro, Lung, H460 - in-vitro, Lung, H1650
TumCG↓, TumMeta↓, Ferroptosis↑, ROS↑, MDA↑, Iron↑, GSH↓, GPx4↓, xCT↓, MMP↓, ATP↓,
575- ART/DHA,    Dihydroartemisinin initiates ferroptosis in glioblastoma through GPX4 inhibition
- in-vitro, GBM, U87MG
GPx4↓, xCT∅, ROS↑, Ferroptosis↑, ACSL4∅,
1410- CUR,    Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway
- vitro+vivo, OS, MG63
tumCV↓, Apoptosis↑, TumCG↓, NRF2↓, GPx4↓, HO-1↓, xCT↓, ROS↑, MDA↑, GSH↓,
2455- erastin,    Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments
- in-vitro, Cerv, HeLa
xCT↓, GSH↓, ROS↑, TumCMig↓,
1204- MET,    Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
MDA↑, ROS↑, Iron↑, GSH↓, T-SOD↓, Catalase↓, GPx4↓, xCT↓, NRF2↓, HO-1↓,
2054- PB,    Sodium butyrate induces ferroptosis in endometrial cancer cells via the RBM3/SLC7A11 axis
- in-vitro, EC, ISH - in-vitro, EC, HEC1B
Ferroptosis↑, xCT↓, RBM3↑, HDAC↓, ROS↑,
1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑, ChemoSen↑, *BioAv↓, *BioAv↑, Ferroptosis↑, lipid-P↑, xCT↓, GPx4↓, *BioAv↑, COX2↓, cycD1/CCND1↓, FasL↓, FOXP3↓, HLA↑, p‑NF-kB↓, BAX↑, Bcl-2↓, MALAT1↓,
2410- SIL,    Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
TumAuto↑, ATP↓, Glycolysis↓, H2O2↑, P53↑, GSH↓, xCT↓, BNIP3↝, MMP↑, mt-ROS↑, mtDam↑, HK2↓, PFKP↓, PKM2↓, TumCG↓,
2198- SK,    Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axis
- in-vitro, OS, MG63 - in-vitro, OS, 143B
TumCP↓, TumCCA↑, Ferroptosis↑, Iron↑, ROS↑, lipid-P↑, MDA↑, mtDam↑, NRF2↓, xCT↓, GPx4↓, GSH/GSSG↓, Keap1↑,
2454- Trip,    Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ
- in-vitro, HNSCC, HaCaT - in-vivo, NA, NA
GSDME-N↑, Pyro↑, cMyc↓, HK2↓, BAD↑, BAX↑, Casp3↑, NRF2↓, xCT↓, ROS↑, eff↑, Glycolysis↓, GlucoseCon↓, lactateProd↓, ATP↓, xCT↓, eff↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   Ferroptosis↑, 5,   GPx4↓, 6,   GSH↓, 5,   GSH/GSSG↓, 1,   H2O2↑, 1,   HO-1↓, 2,   Iron↑, 3,   Keap1↑, 1,   lipid-P↑, 2,   MDA↑, 4,   NRF2↓, 4,   ROS↑, 8,   mt-ROS↑, 1,   T-SOD↓, 1,   xCT↓, 10,   xCT∅, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 3,   MMP↓, 1,   MMP↑, 1,   mtDam↑, 2,  

Core Metabolism/Glycolysis ⓘ

ACSL4∅, 1,   cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 2,   lactateProd↓, 1,   PFKP↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   BAD↑, 1,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↑, 1,   FasL↓, 1,   Ferroptosis↑, 5,   GSDME-N↑, 1,   Pyro↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↝, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1,   TumCG↓, 3,  

Migration ⓘ

HLA↑, 1,   MALAT1↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   FOXP3↓, 1,   p‑NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

RBM3↑, 1,  
Total Targets: 58

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,  
Total Targets: 2

Scientific Paper Hit Count for: xCT, SLC7A11
1 Andrographis
1 Artemisinin
1 Curcumin
1 erastin
1 Metformin
1 Phenylbutyrate
1 Resveratrol
1 Silymarin (Milk Thistle) silibinin
1 Shikonin
1 triptolide
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#:%  Target#:801  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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