| Rank |
Pathway / Target Axis |
Direction |
Primary Effect |
Notes / Cancer Relevance |
Ref |
| 1 |
Thioredoxin / Thioredoxin reductase (Trx / TrxR) |
↓ Trx / TrxR activity |
Redox buffering collapse |
Primary molecular target; covalent cysteine interaction drives loss of antioxidant capacity |
(ref) |
| 2 |
ROS accumulation |
↑ ROS |
Oxidative stress overload |
Immediate consequence of Trx/TrxR inhibition; upstream of mitochondrial damage |
(ref) |
| 3 |
Mitochondrial integrity (ΔΨm) |
↓ ΔΨm |
Mitochondrial dysfunction |
GA reduces mitochondrial membrane potential prior to execution-phase death |
(ref) |
| 4 |
Intrinsic apoptosis / pyroptosis (caspase-3, GSDME) |
↑ programmed cell death |
Execution-phase killing |
Mitochondrial apoptosis and caspase-3/GSDME-dependent pyroptosis reported |
(ref) |
| 5 |
NF-κB signaling |
↓ NF-κB activation |
Reduced pro-survival transcription |
Redox-sensitive suppression of NF-κB nuclear activity and target genes |
(ref) |
| 6 |
PI3K–AKT survival signaling |
↓ AKT phosphorylation |
Survival pathway collapse |
Downstream of oxidative stress and chaperone disruption |
(ref) |
| 7 |
HSP90 chaperone function |
↓ client stabilization |
Oncoprotein destabilization |
GA disrupts HSP90–client interactions affecting AKT, HER2, etc. |
(ref) |
| 8 |
ER stress / UPR |
↑ ER stress signaling |
Proteotoxic stress |
Secondary ER stress response following redox and mitochondrial disruption |
(ref) |
| 9 |
Cell cycle regulation |
↑ cell-cycle arrest |
Proliferation blockade |
Checkpoint activation downstream of stress signaling |
(ref) |
| 10 |
Autophagy (stress-induced) |
↑ autophagy |
Adaptive or pro-death response |
Autophagy induction reported; role varies by context |
(ref) |
| 11 |
Angiogenesis signaling (VEGF) |
↓ VEGF expression |
Anti-angiogenic effect |
Suppression of pro-angiogenic transcription observed |
(ref) |
| 12 |
Tumor growth in vivo |
↓ tumor volume |
Integrated outcome |
Xenograft models show significant tumor growth inhibition |
(ref) |