Juglone / GPx4 Cancer Research Results

JG, Juglone: Click to Expand ⟱
Features:
Found in roots, leaves, nut-hulls, bark and wood of walnut trees.
Juglone (5-hydroxy-1,4-naphthoquinone)
Juglans nigra refers to the black walnut tree, which is one of the most well-known sources of juglone
-Research has focused on the hulls (the green outer covering of the walnut) because they have the highest concentrations.
-Fresh hulls can contain juglone levels in the range of approximately 1–5% of the dry weight

-Juglone can redox cycle to generate reactive oxygen species (ROS).
-Increasing Bax, decreasing Bcl‑2, caspase activation, and MMP depolarization.
-Modulation of MAPK pathways (including ERK, JNK, and p38)
-May inhibit NF‑κB signaling
-Cause DNA damage or stress that, in turn, leads to p53 pathway activation— Pin1 Inhibition
–Pin1, a peptidyl-prolyl cis/trans isomerase, is frequently overexpressed in cancer.

-ic50 maybe 5-10uM
-For matching 5uM, crude estimate is 5mg consumption of juglone required which might be 1.5 g of black walnut hull material

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Redox cycling (quinone–semiquinone system) ↑↑ ROS Oxidative stress overload Juglone can act as a redox-cycling quinone; ROS elevation is a dominant upstream driver in multiple cancer models (ref)
2 Thiol buffering (GSH depletion) ↓ GSH Loss of redox buffering In HL-60 leukemia cells, juglone induces ROS and explicitly depletes GSH; antioxidants block downstream apoptosis markers (ref)
3 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Mitochondrial dysfunction In LNCaP prostate cancer cells, juglone decreases mitochondrial potential (ΔΨ) during intrinsic apoptosis (ref)
4 Intrinsic apoptosis (Caspase-9 → Caspase-3) ↑ Caspase-9/3 activation Programmed cell death Same LNCaP evidence base: intrinsic apoptosis with activation of caspases 3 and 9 is reported for juglone (ref)
5 DNA damage / genotoxic stress ↑ DNA damage Checkpoint activation and death signaling Juglone is reported to have genotoxic effects (DNA damage) in melanoma models, consistent with ROS-driven injury (ref)
6 p53 stress response ↑ p53 pathway (activation) Cell-cycle arrest / apoptosis cooperation Human liver cancer model: juglone drives apoptosis and autophagy via a ROS-mediated p53 pathway (in vitro and in vivo) (ref)
7 MAPK stress pathways (JNK / p38) ↑ JNK / ↑ p38 Pro-death stress signaling Mechanistic synthesis notes juglone induces ROS and activates JNK and p38 MAPK, contributing to cell death signaling (ref)
8 NF-κB signaling ↓ NF-κB Reduced pro-survival transcription Literature reports juglone inhibits NF-κB production/signaling in colonic cancer cell contexts (noted as prior work) (ref)
9 PI3K–AKT survival pathway ↓ PI3K / ↓ p-AKT Survival pathway suppression NSCLC: juglone increases ROS and inhibits PI3K/Akt signaling; NAC (ROS scavenger) attenuates apoptosis and pathway changes (ref)
10 Cell cycle control ↑ arrest Proliferation blockade NSCLC: juglone arrests the cell cycle alongside ROS rise and apoptosis marker changes (ref)
11 Autophagy ↑ autophagy (stress-associated) Stress adaptation / death crosstalk Juglone induces both apoptosis and autophagy in cancer cells via MAPK pathway modulation (with ROS-MAPK coupling) (ref)
12 Angiogenesis signaling (VEGF) ↓ VEGF Reduced vascular support Pancreatic cancer cell lines: juglone reduces VEGF gene expression (and other metastasis/angiogenesis-related genes) at sub-IC50 exposure (ref)


GPx4, Glutathione Peroxidase 4: Click to Expand ⟱
Source:
Type:
GPX4 (Glutathione Peroxidase 4) is a selenoprotein that plays a crucial role in the regulation of ferroptosis, a form of programmed cell death characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS).
GPX4 has been found to be upregulated in several tumor types, promoting cancer cell survival and resistance to therapy. For instance, GPX4 overexpression has been observed in renal cell carcinoma, pancreatic ductal adenocarcinoma, and triple-negative breast cancer, among others. -GPX4 is known as a lipid peroxidation inhibitor protein, and its antioxidant effect is closely related to ferrous iron
Scientific Papers found: Click to Expand⟱
5099- JG,    Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK
- vitro+vivo, GBM, LN229 - vitro+vivo, GBM, T98G
Ferroptosis↑, p‑MAPK↑, NRF2↓, GPx4↓, TumPF↓, Apoptosis↑, ROS↑, GSH↓, lipid-P↑, Ki-67↓, TumCG↓,
1924- JG,    Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway
- in-vitro, Lung, A549
TumCMig↓, TumCI↓, TumCCA↑, Apoptosis↑, cl‑Casp3↑, BAX↑, Cyt‑c↑, ROS↑, MDA↑, GPx4↓, SOD↓, PI3K↓, Akt↓, eff↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 2,   GSH↓, 1,   lipid-P↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 2,   SOD↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 1,   cl‑Casp3↑, 1,   Cyt‑c↑, 1,   Ferroptosis↑, 1,   p‑MAPK↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ki-67↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumPF↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  
Total Targets: 24

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GPx4, Glutathione Peroxidase 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#:105  Target#:643  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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