| Rank |
Pathway / Axis |
Cancer / Tumor Context |
Normal Tissue Context |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
NF-κB inflammatory signaling |
NF-κB ↓; COX-2, IL-6, TNF-α ↓ (reported) |
Inflammation tone ↓ |
R, G |
Anti-inflammatory / anti-survival modulation |
Most consistent mechanistic theme for perilla and rosmarinic-acid–rich fractions. |
| 2 |
Nrf2 / ARE antioxidant response |
Context-dependent modulation |
Nrf2 ↑; HO-1 ↑; GSH systems ↑ |
R, G |
Redox buffering |
Common polyphenol signature; tumor implications vary and may affect therapy sensitivity in some contexts. |
| 3 |
ROS / redox modulation |
ROS ↓ (often) or variable; pro-oxidant effects not dominant |
Oxidative stress ↓ (protective) |
P, R |
Antioxidant-leaning redox modulation |
Perilla is typically antioxidant in inflammatory/oxidative injury models; tumor cytotoxicity is usually weaker than strong pro-oxidants. |
| 4 |
MAPK pathways (ERK / JNK / p38) |
MAPK modulation (context-dependent) |
↔ |
P, R, G |
Signal reprogramming |
Direction varies with extract composition and cell line; often downstream of redox/inflammation shifts. |
| 5 |
PI3K → AKT (± mTOR) |
PI3K/AKT ↓ (reported; model-dependent) |
↔ |
R, G |
Growth/survival modulation |
Often secondary to NF-κB and oxidative stress pathway changes. |
| 6 |
Cell-cycle arrest (G1 / G2-M) |
Cell-cycle arrest ↑ (reported; modest) |
↔ |
G |
Cytostasis |
Phenotype-level effect; strength depends on dose and extract standardization. |
| 7 |
Intrinsic apoptosis (mitochondrial) |
Apoptosis ↑ (reported; modest); caspases ↑ |
↔ (limited activation) |
G |
Conditional cytotoxicity |
Usually not a “direct toxin” signature; more consistent as an anti-inflammatory/antioxidant modulator. |
| 8 |
Angiogenesis signaling (VEGF) |
VEGF ↓ (reported in some systems) |
↔ |
G |
Anti-angiogenic modulation |
Evidence exists but is less consistent than NF-κB/Nrf2 effects. |
| 9 |
Invasion / metastasis (MMPs / EMT) |
MMP2/MMP9 ↓; migration ↓ (reported) |
↔ |
G |
Anti-invasive phenotype |
Often downstream of NF-κB and MAPK modulation; not universal across models. |
| 10 |
Extract variability / bioavailability constraint |
Activity varies by part (leaf/seed), solvent, and standardization |
— |
— |
Translation constraint |
Perilla is best treated as “rosmarinic-rich polyphenol extract”; systemic exposure may not match in-vitro doses. |