Juglone / Iron 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)

Iron, Iron: Click to Expand ⟱

Source:

Type:

Iron is an essential nutrient that is crucial for various cellular processes, including DNA synthesis, cell proliferation, and oxygen transport.
Cancer cells often have increased iron requirements due to their rapid growth and proliferation. Some tumors can acquire iron through various mechanisms, including upregulating iron transport proteins. This can support their growth and survival.
Excess iron can lead to the production of reactive oxygen species (ROS) through Fenton reactions, which can cause oxidative damage to DNA, proteins, and lipids. This oxidative stress can contribute to cancer development and progression.

Scientific Papers found: Click to Expand⟱

1921-

JG,

Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis

in-vitro,

PC,

vitro+vivo,

PC,

TumCG↓, Ferroptosis↑, ROS↑, Iron↑, lipid-P↑, MDA↑, GSH↓, FOSL1↑, HO-1↑,

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:

Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1, GSH↓, 1, HO-1↑, 1, Iron↑, 1, lipid-P↑, 1, MDA↑, 1, ROS↑, 1,

Cell Death ⓘ

Ferroptosis↑, 1,

Proliferation, Differentiation & Cell State ⓘ

FOSL1↑, 1, TumCG↓, 1,
Total Targets: 10

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: Iron, Iron

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