Juglone / GPx 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)

GPx, Glutathione peroxidases: Click to Expand ⟱

Source:

Type:

Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS).
Glutathione peroxidase (GPx) refers to a family of antioxidant enzymes that play a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. There are several isoforms of GPx, including GPx1, GPx2, GPx3, and GPx4, each with distinct tissue distributions and functions.
GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers.

GPx expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.

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: GPx, Glutathione peroxidases

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

Juglone / GPx 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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