Juglone / Casp3 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)


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
5115- JG,    Natural Products to Fight Cancer: A Focus on Juglans regia
- Review, Var, NA
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↓,
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↓,
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↓,
1918- JG,    ROS -mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro
- in-vitro, Liver, HepG2 - in-vivo, NA, NA
TumCG↓, TumCP↓, Apoptosis↑, TumAuto↑, AMPK↑, mTOR↑, P53↑, H2O2↑, ROS↑, toxicity↝, p62↓, DR5↑, Casp8↑, PARP↑, cl‑Casp3↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   Catalase↓, 1,   GPx↓, 1,   GPx4↓, 1,   GSH↓, 3,   H2O2↑, 1,   lipid-P↑, 1,   MDA↑, 1,   ROS↑, 5,   SOD↓, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 3,   BAX↑, 3,   Bcl-2↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 2,   proCasp3↑, 1,   Casp8↑, 1,   Casp9↑, 2,   proCasp9↑, 1,   Cyt‑c↑, 3,   Diablo↑, 1,   DR5↑, 1,   Fas↑, 1,  

Autophagy & Lysosomes ⓘ

p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   PARP↑, 1,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   GSK‐3β↓, 1,   mTOR↑, 1,   PI3K↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   SMAD2↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 2,   eff↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

Pin1↓, 2,   toxicity↝, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 61

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
5 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#:42  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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