Juglone / TumAuto 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)


TumAuto, Tumor autophagy: Click to Expand ⟱
Source: HalifaxProj(activate)
Type:
Autophagy genes, including Atg3, Atg5, Atg6, Atg7, Atg10, Atg12, and Atg17.
Tumor autophagy refers to the process by which cancer cells degrade and recycle cellular components through autophagy, a cellular mechanism that helps maintain homeostasis and respond to stress. Autophagy can have dual roles in cancer, acting as both a tumor suppressor and a promoter, depending on the context.
Authophagy is the process used by cancer cells to “self-eat” to survive. Authophagy can be both good and bad. If authophagy is prolonged this will become a lethal process to cancer. On the other hand, for a short while (e.g. during chemotheraphy, radiotheraphy, etc.) authophagy is used by cancer cells to survive.
For example, Chloroquine is a blocker of autophagy and has been used in a lab setting to dramatically enhance tumor response to radiotherapy, chemotherapy.
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↑,
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↑,
1917- JG,    Inhibition of human leukemia cells growth by juglone is mediated via autophagy induction, endogenous ROS production, and inhibition of cell migration and invasion
- in-vitro, AML, HL-60
selectivity↑, LC3I↑, LC3II↑, Beclin-1↑, ROS↑, tumCV↓, Dose↝, TumAuto↑,

Showing Research Papers: 1 to 4 of 4

* 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 ⓘ

H2O2↑, 2,   ROS↑, 3,   m-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,  

Cell Death ⓘ

Apoptosis↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 1,   DR5↑, 1,   JNK↑, 1,   MAPK↑, 1,   p38↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   LC3I↑, 1,   LC3II↑, 2,   p62↓, 1,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   PARP↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↑, 2,   TumCG↓, 2,  

Migration ⓘ

TumCP↓, 2,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,   selectivity↑, 1,  

Functional Outcomes ⓘ

toxicity↝, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumAuto, Tumor autophagy
4 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#:321  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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