Juglone / Ca+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)


Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
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↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   GSH↓, 1,   lipid-P↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   BAX↑, 2,   Bcl-2↓, 2,   Casp3?, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 2,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Migration ⓘ

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

Functional Outcomes ⓘ

Pin1↓, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 20

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
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#:38  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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