| Rank |
Pathway / Target Axis |
Direction |
Primary Effect |
Notes / Cancer Relevance |
Ref |
| 1 |
GSH / thiol buffering (PEITC–GSH conjugation → GSH depletion) |
↓ GSH |
Upstream redox collapse |
PEITC drives a GSH-iron-ROS axis; GSH depletion is upstream of multiple death programs |
(ref) |
| 2 |
ROS accumulation |
↑ ROS |
Oxidative stress trigger |
PEITC increases intracellular ROS, which then drives mitochondrial disruption and apoptosis |
(ref) |
| 3 |
Ferroptosis (lipid peroxidation; anti-ferroptotic machinery overwhelmed) |
↑ ferroptosis |
Iron-dependent oxidative death |
Direct evidence that PEITC induces ferroptosis (alongside other death programs) via GSH-iron-ROS mechanisms |
(ref) |
| 4 |
Mitochondrial integrity (ΔΨm; cytochrome-c release) |
↓ ΔΨm / ↑ cytochrome-c release |
Mitochondrial dysfunction |
PEITC promotes ROS, decreases ΔΨm, increases cytochrome-c release in cancer cells |
(ref) |
| 5 |
Intrinsic apoptosis (caspase-9 → caspase-3) |
↑ caspase activation / ↑ apoptosis |
Execution-phase cell death |
PEITC activates caspase-9 and caspase-3 and induces apoptosis downstream of mitochondrial dysfunction |
(ref) |
| 6 |
Akt → JNK → Mcl-1 axis |
↓ Akt / ↑ JNK / ↓ Mcl-1 |
Pro-survival signaling collapse |
Leukemia study: PEITC-initiated death is linked to Akt inactivation → JNK activation → Mcl-1 downregulation |
(ref) |
| 7 |
NF-κB signaling |
↓ NF-κB transcriptional activity / ↓ p65 nuclear translocation |
Reduced pro-survival / inflammatory transcription |
PEITC inhibits NF-κB activity and NF-κB–regulated genes (e.g., cyclin D1, VEGF, Bcl-xL) in prostate cancer cells |
(ref) |
| 8 |
JAK–STAT3 signaling |
↓ STAT3 activation |
Reduced survival / growth signaling |
PEITC inhibits IL-6–driven JAK–STAT3 activation in prostate cancer cells (STAT3 signaling direction shown) |
(ref) |
| 9 |
Cell-cycle regulation |
↑ G2/M arrest |
Proliferation blockade |
PEITC inhibits proliferation and induces G2/M cell-cycle arrest in prostate cancer cells |
(ref) |
| 10 |
Autophagy program |
↑ autophagy |
Stress response (can interact with death) |
PEITC induces autophagy along with ferroptosis and apoptosis in osteosarcoma cells |
(ref) |
| 11 |
Migration / invasion (MMPs, FAK, RhoA) |
↓ migration & invasion / ↓ MMPs |
Anti-metastatic phenotype |
PEITC suppresses migration/invasion and downregulates MMP-2/-7/-9 and motility regulators (FAK, RhoA) |
(ref) |
| 12 |
In vivo anti-tumor effect |
↓ tumor burden / ↑ survival (model-dependent) |
Demonstrated efficacy in animal model |
Leukemia study reports PEITC anti-leukemic activity including mechanistic signaling changes and in vivo efficacy evidence |
(ref) |