Database Query Results : erastin, , xCT

erastin, erastin: Click to Expand ⟱
Features:
Erastin is often referred to as a "metabolic inhibitor" or a "ferroptosis inducer", rather than a traditional chemotherapy agent.
Erastin is primarily available as a research chemical—it's not an approved therapeutic for clinical use.

Pathways:
-Erastin inhibits system xCT, thereby reducing cystine uptake. This leads to decreased intracellular cysteine, a precursor for GSH. As a consequence, the cell’s glutathione levels drop, compromising its ability to neutralize reactive oxygen species (ROS).
-Glutathione (GSH) Depletion and Increased Oxidative Stress
-Voltage-Dependent Anion Channels (VDACs): Altering VDAC function can affect mitochondrial metabolism, leading to changes in energy production and further enhancing oxidative stress.
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⟱
2455- erastin,    Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments
- in-vitro, Cerv, HeLa
xCT↓, targeted inhibitors have been developed, such as erastin
GSH↓, erastin significantly reduced intracellular GSH levels in HeLa cells
ROS↑, erastin significantly increased intracellular ROS levels in HeLa cells
TumCMig↓, erastin significantly inhibited the migration activity of HeLa cells,

5046- erastin,  SAS,    The structure of erastin-bound xCT–4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis
- Study, Var, NA
xCT↓, reduced by the system xc– inhibitors, erastin and sulfasalazine
ROS↑, moreover, inhibiting xCT impairs cystine uptake, causing an accumulation of ROS and suppressing tumor growth.
TumCG↓,
GSH↓, Erastin functions by inhibiting the import of cystine, thereby depleting intracellular glutathione (GSH), which serves as a necessary cofactor for the enzyme glutathione peroxidase 4 (GPX4) in eliminating lipid peroxides
Ferroptosis↑, erastin is commonly used to induce ferroptosis, particularly in cultured cells.

5047- erastin,    The ferroptosis inducer erastin irreversibly inhibits system xc− and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells
- in-vitro, Ovarian, NA
xCT↓, erastin was reported to target and inhibit system xc−, leading to cysteine starvation, glutathione depletion and consequently ferroptotic cell death.
GSH↓,
Ferroptosis↑,
ChemoSen↑, More importantly, short exposure of tumor cells with erastin strongly potentiated the cytotoxic effects of cisplatin to efficiently eradicate tumor cells.
eff↑, only a very short pre-treatment of erastin suffices to synergize with cisplatin to efficiently induce cancer cell death

5048- erastin,    How erastin assassinates cells by ferroptosis revealed
- Review, Var, NA
Ferroptosis↑, erastin can induce a form of iron-dependent cell death by inhibiting system Xc−-mediated cystine import; they further coined a term ferroptosis to highlight the iron-dependent nature of this cell death
xCT↓,
lipid-P↑, When erastin blocks the transporter activity of system Xc−, the collapse of ferroptosis defense systems leads to the excessive accumulation of lipid peroxides on cell membranes and subsequent ferroptotic cell death


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 3,   GSH↓, 3,   lipid-P↑, 1,   ROS↑, 2,   xCT↓, 4,  

Cell Death ⓘ

Ferroptosis↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Migration ⓘ

TumCMig↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,  
Total Targets: 10

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: xCT, SLC7A11
4 erastin
1 Sulfasalazine
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#:241  Target#:801  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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