Juglone / FOSL1 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)

FOSL1, FOSL1 (FRA-1): Click to Expand ⟱

Source:

Type:

FOSL1 (FRA-1)
FOSL1 is a member of the activator protein-1 (AP-1) transcription factor complex. It is involved in regulating genes that control proliferation, differentiation, survival, and metastasis.

– Observations: Overexpression of FOSL1 has been associated with aggressive subtypes, epithelial–mesenchymal transition (EMT), and increased invasiveness.

– Prognostic Implication: Higher FOSL1 levels often correlate with poorer overall survival and disease 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: FOSL1, FOSL1 (FRA-1)

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