| 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) |