xCT/SLC7A11 Cancer Research Results

xCT/SLC7A11, Solute Carrier Family 7 Member 11: 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⟱
5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1/ATG6↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT/SLC7A11↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

6983- Form,    Formononetin enhances angiogenesis in diabetic wounds by inhibiting ferroptosis through suppression of mtROS-mediated xCT/GPX4 upregulation
- vitro+vivo, Nor, HUVECs - vitro+vivo, Diabetic, NA
*BloodF↑, Formononetin (FMN), a phytoestrogen from Astragalus roots, is traditionally used to enhance blood function and microcirculation; however, its mechanism remains unclear.
*Ferroptosis↓, FMN effectively reduced ferroptosis markers in HG-treated HUVECs,
*eff↓, and Erastin treatment abolished this protective effect.
*mtDam↓, block ferroptosis through two mechanisms: restoration of mitochondrial integrity and reactivation of the xCT/GPX4 antioxidant system
*xCT/SLC7A11↑,
*GPx4↑,
*Wound Healing↑, When we tested FMN in diabetic mice, wound closure rates improved substantially, the expression of xCT and GPX4 was increased, and CD31 expression in wound vessels increased, which matched what we observed in vitro.
*CD31/PECAM-1↑,
*mt-ROS↓, mitigation of mitochondrial reactive oxygen species (mtROS) accumulation through xCT/GPX4 activation.

7766- ISL,    Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice
- in-vivo, Stroke, NA
*ROS↓, ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity,
*MDA↓,
*LDH↑,
*SOD↑,
*Catalase↑,
*NRF2↑, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage.
*i-Iron↓, ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis.
*GPx4↑,
*xCT/SLC7A11↑,
*lipid-P↓,
*Ferroptosis↓,
*HO-1↑, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4
*ACSL4↓,
*mtDam↓, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R.
*Stroke↓,

8054- KAE,    Kaempferol Improves Alzheimer's Disease by Inhibiting Neuronal Ferroptosis via Activating GPX4/AKR1C3 Signaling Pathway
- vitro+vivo, AD, NA
*AKR1B10↝, Kaempferol treatment facilitated the expression of AKR1B1 in PC12 cells exposed to Aβ1–42
*MDA↓, Kaempferol treatment mitigated the Aβ1–42‐induced increases in Fe2+, MDA, and lipid ROS and Aβ1–42‐induced decreases in GSH synthesis and SOD activity.
*ROS↓,
*GSH↑,
*SOD↑,
*GPx4↑, The reduction in ferroptosis‐related proteins (GPX4, NQO1, SLC7A11, AKR1C1, and AKR1C3) and the inhibition of Nrf2 nuclear translocation and Nrf2/HO‐1 signaling caused by Aβ1–42 were also reversed by kaempferol.
*NQO1↑,
*xCT/SLC7A11↑,
*NRF2↑,
*HO-1↑,
*cognitive↑, In vivo studies revealed that kaempferol improved cognitive impairments, reduced deposition of Aβ and p‐Tau, and alleviated neuronal ferroptosis in the hippocampal tissues of an AD mouse model
*Aβ↓,
*p‑tau↓,
*Ferroptosis↓,
*AKR1C3/17β-HSD5/PGF Synthase↑, inhibiting neuronal ferroptosis through the activation of the Nrf2/HO‐1/GPX4/AKR1C3 signaling via upregulation of AKR1B1
*AKR1B1/ALR2↑,

8055- KAE,    Molecular Mechanisms of the Anticancer Activity of the Flavonoid Kaempferol: A Comprehensive Review
- Review, Var, NA
antiNeop↑, Kaempferol (KAE), a natural flavonoid, has emerged as a promising multi-target antineoplastic agent characterized by high efficacy and minimal systemic toxicity.
*toxicity↓,
TumCCA↑, KAE orchestrates tumor eradication by enforcing cell cycle arrest across multiple phases and triggering a complex, interconnected network of programmed cell death.
ROS↑, We highlight how reactive oxygen species and endoplasmic reticulum stress serve as central upstream nodes driving the mechanistic crosstalk among apoptosis, lethal autophagy, gasdermin E-mediated pyroptosis, and ferroptosis.
ER Stress↑,
TumAuto↑,
Pyro↑,
Ferroptosis↑,
angioG↓, KAE actively remodels the tumor microenvironment by inhibiting angiogenesis and repolarizing tumor-associated macrophages, thereby converting immunosuppressive "cold" tumors into immune-active "hot" tumors.
Imm↝,
eff↑, this review introduces the emerging prebiotic-like crosstalk between KAE and the gut microbiome, providing a strong mechanistic rationale for its synergistic application with immune checkpoint inhibitors.
ChemoSen↑, As a potent chemosensitizer, KAE also overcomes multidrug resistance and mitigates chemotherapy-induced toxicities.
MPT↑, This leads to the opening of the mitochondrial permeability transition (MPTP) pore and the collapse of the mitochondrial membrane potential (ΔΨm).
MMP↓,
mtDam↑, damaged mitochondria release pro-apoptotic factors, including cytochrome c, into the cytoplasm, inducing the formation of the apoptosome.
Cyt‑c↑,
Bax:Bcl2↑, upregulation of the Bax/Bcl-2 ratio.
Fas↑, demonstrated that in colorectal cancer models, KAE treatment significantly upregulates the expression of membrane-bound FAS ligand.
DR4↑, KAE directly upregulates the expression of death receptor 4 and death receptor 5 in human ovarian cancer cells (OVCAR-3 and SKOV-3) by activating the JNK/ERK-CHOP signaling pathway.
DR5↑,
JNK↑,
ERK↑,
CHOP/DDIT3↑,
ER Stress↑, Studies have shown that KAE possesses significant ERS-inducing activity, leading to the pathological accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER) lumen, which in turn triggers a persistent unfolded protein resp
UPR↑,
Ca+2↑, accumulated cytosolic Ca²+ acts as a central apoptotic signal
PI3K↓, The inhibition of the PI3K/Akt/mTOR pathway is a primary mechanism for this effect.
Akt↓,
mTOR↓,
AMPK↑, Conversely, KAE reactivates the AMPK pathway.
*Ferroptosis↓, KAE acts as a potent antioxidant in normal tissues to prevent ferroptosis-induced injury.
*antiOx↑,
*NRF2↑, KAE effectively suppresses ferroptosis by strongly activating the Nrf2/glutathione peroxidase 4 (GPX4) antioxidant axis.
*GPx4↑,
*ROS↓, It actively reduces intracellular ROS, malondialdehyde, and iron (Fe²+) accumulation while upregulating the protective SLC7A11 transporter
*MDA↓,
*i-Iron↓,
*xCT/SLC7A11↑,
VEGF↓, KAE not only inhibits VEGF expression driven by hypoxia-inducible factor-1α (HIF-1α) but also simultaneously blocks the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition (EMT) process
Wnt↓,
β-catenin/ZEB1↓,
EMT↓,
STAT3↓, KAE blocks the persistent activation of the STAT3 signaling pathway, leading to the downregulation of M2 phenotypic markers and the inhibition of the inflammatory chemokine CCL2 release.
M2 MC↓,
MCP1/CCL2↓,
MMP9↓, thereby downregulating the protein expression and enzymatic activity of MMP-9.
MMP2↓, in tongue squamous cell carcinoma models, KAE inhibits the expression of MMP-2 and its tissue inhibitor, TIMP-2, at the transcriptional level
TIMP2↓,
ChemoSen↑, When combined with classical chemotherapeutics, KAE functions as a potent sensitizer, amplifying the lethal effects of the drugs through complementary signaling networks.
PKM2↑, In colorectal cancer cells, KAE promotes the expression of microRNA-326 (miR-326), which directly targets the 3′-UTR of the pyruvate kinase M2 (PKM2) isoform to inhibit glycolysis.
Glycolysis↓,
CSCs↓, profound chemosensitizing effect by downregulating core stemness transcription factors (such as SOX2 and OCT4) and disrupting the CD44-NANOG-MDR1 resistance complex
SOX4↓,
OCT4↓,
CD44↓,
Nanog↓,
MDR1↓,
*GutMicro↑, KAE exerts a remarkable prebiotic-like effect by remodeling the architectural composition of the gut microbiota

5096- SSE,    Selenium Toxicity Accelerated by Out-of-Control Response of Nrf2-xCT Pathway
- in-vitro, BC, MCF7
xCT/SLC7A11↑, Expression of xCT mRNA was remarkably increased in MCF-7 cells after Se treatment, which may further increase Se uptake and oxidative stress.
ROS↑,
NRF2↑, Oxidative stress activates Nrf2 regulon containing GSH biosynthesis enzymes and xCT. Therefore, further Se is taken into the cell, more ROS is generated, and xCT is induced again.

5094- SSE,    Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System
- vitro+vivo, Nor, NRK52E
*GPx4↑, SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels.
*xCT/SLC7A11↑,
*GSH↑, SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.
*RenoP↑,


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↓, 1,   Ferroptosis↑, 1,   GSH↓, 1,   MDA↑, 1,   NRF2↑, 1,   ROS↑, 3,   xCT/SLC7A11↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   MMP↓, 1,   MPT↑, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   Glycolysis↓, 1,   HK2↓, 1,   PKM2↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Bax:Bcl2↑, 1,   Cyt‑c↑, 1,   DR4↑, 1,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   JNK↑, 1,   Pyro↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

AMPKα↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   ER Stress↑, 2,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

p‑Beclin-1/ATG6↑, 1,   TumAuto↑, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   FOXO3↑, 1,   mTOR↓, 1,   Nanog↓, 1,   OCT4↓, 1,   PI3K↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   MMP2↓, 1,   MMP9↓, 1,   SOX4↓, 1,   TIMP2↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↝, 1,   M2 MC↓, 1,   MCP1/CCL2↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 2,   Dose↝, 1,   eff↓, 1,   eff↑, 2,   MDR1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

antiNeop↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AKR1B1/ALR2↑, 1,   AKR1B10↝, 1,   AKR1C3/17β-HSD5/PGF Synthase↑, 1,   Stroke↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   Ferroptosis↓, 4,   GPx4↑, 5,   GSH↑, 2,   HO-1↑, 2,   i-Iron↓, 2,   lipid-P↓, 1,   MDA↓, 3,   NQO1↑, 1,   NRF2↑, 3,   ROS↓, 3,   mt-ROS↓, 1,   SOD↑, 2,   xCT/SLC7A11↑, 5,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mtDam↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4↓, 1,   LDH↑, 1,  

Cell Death(tgid=5) ⓘ

Ferroptosis↓, 4,  

Migration(tgid=13) ⓘ

CD31/PECAM-1↑, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

p‑tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

BloodF↑, 1,   GutMicro↑, 1,   LDH↑, 1,  

Functional Outcomes(tgid=23) ⓘ

cognitive↑, 1,   RenoP↑, 1,   toxicity↓, 1,   Wound Healing↑, 1,  
Total Targets: 34

Scientific Paper Hit Count for: xCT/SLC7A11, Solute Carrier Family 7 Member 11
2 Kaempferol
2 Selenite (Sodium)
1 3-bromopyruvate
1 cetuximab
1 Formononetin
1 Isoliquiritigenin
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

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