Juglone / Bcl-2 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)


Bcl-2, B-cell CLL/lymphoma 2: Click to Expand ⟱
Source: HalifaxProj (inhibit) CGL-Driver Genes
Type: Antiapoptotic Oncogene
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.
Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.
Scientific Papers found: Click to Expand⟱
1926- JG,    Mechanism of juglone-induced apoptosis of MCF-7 cells by the mitochondrial pathway
- in-vitro, BC, MCF-7
TumCG↓, ROS↑, MMP↓, i-Ca+2↑, BAX↑, Bcl-2↓, Cyt‑c↑, Casp3?,
5113- JG,    Juglone in Oxidative Stress and Cell Signaling
- Review, Var, NA - Review, AD, NA
ROS↑, Pin1↓, antiOx⇅, *ROS↓, SMAD2↓, GSH↓, lipid-P↑, TumCCA↓, BAX↑, Bcl-2↓, Casp3↑, Casp9↑, Ca+2↑, Cyt‑c↑, AntiFungal↑, Bacteria↓, Akt↓,
1927- JG,    Juglone-induced apoptosis in human gastric cancer SGC-7901 cells via the mitochondrial pathway
- in-vitro, GC, SGC-7901
Apoptosis↑, ROS↑, Bcl-2↓, BAX↑, MMP↓, Cyt‑c↑, Casp3?, Bax:Bcl2↑,
1923- JG,    Mechanism of Juglone-Induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells
- in-vitro, Endo, NA
TumCP↓, TumCCA↑, cycA1/CCNA1↓, ROS↑, P21↑, CDK2↓, CDK1↓, CDC25↓, Bcl-2↓, Bcl-xL↓, BAX↑, BAD↑, Cyt‑c↑,

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 ⓘ

antiOx⇅, 1,   GSH↓, 1,   lipid-P↑, 1,   ROS↑, 4,  

Mitochondria & Bioenergetics ⓘ

CDC25↓, 1,   MMP↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAD↑, 1,   BAX↑, 4,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Bcl-xL↓, 1,   Casp3?, 2,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 4,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   cycA1/CCNA1↓, 1,   P21↑, 1,   TumCCA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   i-Ca+2↑, 1,   SMAD2↓, 1,   TumCP↓, 1,  

Functional Outcomes ⓘ

Pin1↓, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 31

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Bcl-2, B-cell CLL/lymphoma 2
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#:27  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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