ACSL4 Cancer Research Results
ACSL4, Acyl-CoA Synthetase Long-Chain Family Member 4: Click to Expand ⟱
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ACSL4 (Acyl-CoA Synthetase Long-Chain Family Member 4) is a protein that plays a crucial role in the regulation of fatty acid metabolism, particularly in the context of cancer.
ACSL4 has been shown to be highly expressed in various types of cancer.
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Scientific Papers found: Click to Expand⟱
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms
*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju
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in-vitro, |
GBM, |
U87MG |
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in-vitro, |
Nor, |
HMC3 |
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TumCG↓,
TumCP↓,
TumCCA↑, remarkably reduced S phase in the U87-MG cells (opposite on normal cells)
PCBP1↓,
GSH↓,
GPx4↓,
Beclin-1↑,
MDA↑,
ACSL4↑,
Casp3↑,
Casp7↑,
Ferroptosis↑,
*toxicity↓, exhibited selectivity by having an opposite effect on normal cells (HMC3).
eff↑, The results indicated that low doses of celastrol (0.7 μM) alone do not inhibit proliferation in NPC cells. However, when combined with curcumin, there is a significant enhancement of the antiproliferative effect.
TumCP↓,
GPx4↓, while notably decreasing solute carrier family 7 member 11 and glutathione peroxidase 4,
eff↑, combined treatment exhibited significant antitumor efficacy with low toxic side effects in a xenograft model.
TumAuto↑, Combined Treatment with Curcumin and Low-Dose Celastrol Induced Autophagy in the CNE1 Cell Line
Ferroptosis↑, Ferroptosis Plays a Critical Role in Low-Dose Celastrol Plus Curcumin-Induced Cell Death
Dose↝, more significant decrease observed in cells treated with 0.7 μM celastrol combined with 35 μM curcumin
ACSL4↑, Only the combination of 0.7 μM celastrol and 35 μM curcumin led to a significant increase in ACSL4 levels
toxicity↓, The Combination of Celastrol and Curcumin Demonstrates a Significant Tumor-Suppressive Effect with Low Toxicity
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in-vitro, |
NSCLC, |
A549 |
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in-vitro, |
NSCLC, |
H1299 |
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TumCP↓, EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining
Ki-67↓,
GPx4↓, EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4).
ACSL4↑,
Iron↑, accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis.
MDA↑,
ROS↑,
Ferroptosis↑,
eff↑, The cooperative effect of metformin and EGCG-activated Nrf2/HO-1 signaling pathway, facilitated by SIRT1-mediated Nrf2 deacetylation, enhances the susceptibility of NSCLC to EGCG modulation by promoting reactive oxygen species (ROS) generation and a
NRF2↑,
HO-1↑,
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vitro+vivo, |
GC, |
HGC27 |
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vitro+vivo, |
GC, |
MKN45 |
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TumCP↓, PSO impeded GC cell proliferation, migration, invasion, and growth in vivo.
TumCMig↓,
TumCI↓,
TumCG↓,
*toxicity↓, PSO exhibited no significant toxic effects on organs and mitigated DDP-mediated liver and kidney injuries.
eff↑, The combination of PSO and DDP exhibited enhanced inhibitory functions
Ferroptosis↑, PSO and DDP can significantly promote GC cell ferroptosis.
ACSL4↑, PSO promoted ACSL4 expression and suppressed GPX4, AIFM2, and SLC7A11.
GPx4↓,
ChemoSen↑, PSO may serve as a nontoxic adjuvant to enhance DDP’s efficacy and reduce side effects in GC.
chemoP↑,
AntiTum↑, Moreover, we found that the combination of PSO and DDP had synergistic antitumor effects on GC.
Sepsis↓, PSO has protective effects against sepsis-induced acute lung injury [40] and myocardial injury [41] at a dose of 50 mg/kg.
Showing Research Papers: 1 to 6 of 6
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Catalase↓, 1, Ferroptosis↑, 5, GPx4↓, 5, GSH↓, 3, HO-1↓, 1, HO-1↑, 1, Iron↑, 1, c-Iron↑, 1, lipid-P↓, 1, lipid-P↑, 1, MDA↓, 1, MDA↑, 2, NRF2↑, 1, ROS↑, 3, SOD↑, 1,
Mitochondria & Bioenergetics ⓘ
MMP↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
ACSL4↑, 6,
Cell Death ⓘ
Akt↓, 1, APAF1↑, 1, Apoptosis↑, 2, BAX↑, 1, Bcl-2↓, 1, Casp↑, 1, Casp3↓, 1, Casp3↑, 1, Casp7↑, 1, Casp9↑, 1, Cyt‑c↓, 1, Cyt‑c↑, 1, Ferroptosis↑, 5, iNOS↓, 1, JNK↓, 1, MAPK↓, 1,
Transcription & Epigenetics ⓘ
other↓, 1,
Protein Folding & ER Stress ⓘ
HSP27↓, 1,
Autophagy & Lysosomes ⓘ
ATG5↑, 1, Beclin-1↑, 2, LC3I↑, 1, TumAuto↑, 1,
DNA Damage & Repair ⓘ
DNAdam↑, 2, P53↑, 1,
Cell Cycle & Senescence ⓘ
cycD1/CCND1↓, 1, TumCCA↑, 2,
Proliferation, Differentiation & Cell State ⓘ
CD44↓, 1, EMT↓, 1, ERK↓, 1, GSK‐3β↓, 1, mTOR↓, 1, NOTCH1↓, 1, PI3K↓, 1, TumCG↓, 3, Wnt↓, 1,
Migration ⓘ
Ki-67↓, 1, PCBP1↓, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 5, Vim↓, 1, β-catenin/ZEB1↓, 2,
Barriers & Transport ⓘ
P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, CXCR4↓, 1, IFN-γ↓, 1, IL12↑, 1, IL2↓, 1, IL2↑, 1, IL4↓, 1, Imm↑, 2, NF-kB↓, 1, PD-L1↓, 1, TNF-α↑, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, ChemoSen↑, 5, Dose↝, 2, eff↑, 6, MDR1↓, 1, RadioS↑, 1,
Clinical Biomarkers ⓘ
Ki-67↓, 1, PD-L1↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 1, AntiTum↑, 1, chemoP↑, 2, QoL↑, 1, toxicity↓, 1,
Infection & Microbiome ⓘ
Sepsis↓, 1,
Total Targets: 86
Pathway results for Effect on Normal Cells:
Immune & Inflammatory Signaling ⓘ
Inflam↓, 1,
Functional Outcomes ⓘ
Pain↓, 1, toxicity↓, 2, Wound Healing↑, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1, Diar↓, 1,
Total Targets: 6
Scientific Paper Hit Count for: ACSL4, Acyl-CoA Synthetase Long-Chain Family Member 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#:% Target#:867 State#:% Dir#:2
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