Juglone / AR 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)

AR, androgen receptor: Click to Expand ⟱

Source: HalifaxProj(suppress signaling);CGL-Driver Genes

Type: Oncogene

Androgens play an important role in the proliferation, differentiation, maintenance and function of the prostate [1]. Intriguingly, they may also be involved in the development and progression of prostate cancer. Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen.

The prognostic significance of androgen receptor expression varies widely across different cancer types. In some cancers, high AR expression is associated with poor outcomes, while in others, it may indicate a better prognosis
High expression with poor prognosis is most common.

AR is used as a clinical biomarker for prostate therapy

Scientific Papers found: Click to Expand⟱

5115-

JG,

Natural Products to Fight Cancer: A Focus on Juglans regia

Review,

Var,

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↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

Pin1↓, 1,
Total Targets: 30

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: AR, androgen receptor

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#:15  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

Juglone / AR Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

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