Juglone / Cyt‑c 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)


Cyt‑c, cyt-c Release into Cytosol: Click to Expand ⟱
Source:
Type:
Cytochrome c
** The term "release of cytochrome c" ** an increase in level for the cytosol.
Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis.

The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.
In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.
Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.
Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.
The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.

On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.
On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.
Overexpressed in Breast, Lung, Colon, and Prostrate.
Underexpressed in Ovarian, and Pancreatic.
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?,
5114- JG,    Juglone, from Juglans mandshruica Maxim, inhibits growth and induces apoptosis in human leukemia cell HL-60 through a reactive oxygen species-dependent mechanism
- in-vitro, AML, HL-60
ROS↑, GSH↓, eff↓, cl‑PARP↑, proCasp3↑, proCasp9↑, MMP↓, Cyt‑c↑, Diablo↑,
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↑,
1924- JG,    Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway
- in-vitro, Lung, A549
TumCMig↓, TumCI↓, TumCCA↑, Apoptosis↑, cl‑Casp3↑, BAX↑, Cyt‑c↑, ROS↑, MDA↑, GPx4↓, SOD↓, PI3K↓, Akt↓, eff↓,
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 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   GPx4↓, 1,   GSH↓, 2,   lipid-P↑, 1,   MDA↑, 1,   ROS↑, 6,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

CDC25↓, 1,   MMP↓, 3,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   BAD↑, 1,   BAX↑, 5,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Bcl-xL↓, 1,   Casp3?, 2,   Casp3↑, 1,   cl‑Casp3↑, 1,   proCasp3↑, 1,   Casp9↑, 1,   proCasp9↑, 1,   Cyt‑c↑, 6,   Diablo↑, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   cycA1/CCNA1↓, 1,   P21↑, 1,   TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   TumCG↓, 1,  

Migration ⓘ

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

Drug Metabolism & Resistance ⓘ

eff↓, 2,  

Functional Outcomes ⓘ

Pin1↓, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Cyt‑c, cyt-c Release into Cytosol
6 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#:77  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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