Juglone / Apoptosis 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)


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.
Scientific Papers found: Click to Expand⟱
5118- JG,    Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells
- in-vitro, HCC, HepG2
m-ROS↑, DNAdam↑, Apoptosis↑, TumAuto↑, p38↑, MAPK↑, JNK↑, MMP↓, LC3II↑, Beclin-1↑,
5117- JG,    https://pubmed.ncbi.nlm.nih.gov/31283929/
- vitro+vivo, Liver, NA
TumCG↓, TumCP↓, Apoptosis↑, TumAuto↑, AMPK↑, mTOR↑, P53↑, H2O2↑, ROS↑,
5115- JG,    Natural Products to Fight Cancer: A Focus on Juglans regia
- Review, Var, NA
Casp3↑, Casp9↑, MMP↓, AR↓, PSA↓, E-cadherin↑, N-cadherin↓, Vim↓, Akt↓, GSK‐3β↓, EMT↑, TumCI↓, MMP9↓, VEGF↓, MMP2↓, TumCCA↑, ROS↑, Apoptosis↑, GSH↓, Catalase↓, SOD↓, GPx↓, DNAdam↑, γH2AX↑, eff↑, BAX↑, Fas↑, Pin1↓,
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↓,
1927- JG,    Juglone-induced apoptosis in human gastric cancer SGC-7901 cells via the mitochondrial pathway
- in-vitro, GC, SGC-7901
Apoptosis↑, ROS↑, Bcl-2↓, BAX↑, MMP↓, Cyt‑c↑, Casp3?, Bax:Bcl2↑,
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↓,
1922- JG,    Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma
- in-vitro, GBM, U87MG
tumCV↓, TumCP↓, ROS↑, p‑p38↑, eff↓, Apoptosis↑, OS↑,
1919- JG,    The Anti-Glioma Effect of Juglone Derivatives through ROS Generation
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
ROS↑, Apoptosis↑, eff↓, eff↓,
1918- JG,    ROS -mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro
- in-vitro, Liver, HepG2 - in-vivo, NA, NA
TumCG↓, TumCP↓, Apoptosis↑, TumAuto↑, AMPK↑, mTOR↑, P53↑, H2O2↑, ROS↑, toxicity↝, p62↓, DR5↑, Casp8↑, PARP↑, cl‑Casp3↑,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   Ferroptosis↑, 1,   GPx↓, 1,   GPx4↓, 2,   GSH↓, 2,   H2O2↑, 2,   lipid-P↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 8,   m-ROS↑, 1,   SOD↓, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 9,   BAX↑, 3,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3?, 1,   Casp3↑, 1,   cl‑Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 2,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↑, 1,   p‑MAPK↑, 1,   p38↑, 1,   p‑p38↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 2,   PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   GSK‐3β↓, 1,   mTOR↑, 2,   PI3K↓, 1,   TumCG↓, 3,  

Migration ⓘ

E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 3,   TumPF↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 4,   eff↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   Ki-67↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   Pin1↓, 1,   toxicity↝, 1,  
Total Targets: 69

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Apoptosis, Apoptosis
9 Juglone
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#:14  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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