| Rank |
Pathway / Axis |
Cancer Cells |
Normal Cells |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
Mitochondrial apoptosis program |
Bax↑; Bcl-2↓; caspases↑ (model-dependent) |
↔ / protective (context-dependent) |
R/G |
Pro-apoptotic shift |
Bax↑ and Bcl-2↓ in MCF-7 with AV extract; many “direct anticancer” claims are extract- or anthraquinone-driven and preclinical. |
| 2 |
PI3K/AKT/mTOR survival signaling |
↓ (model-dependent) |
↔ |
R/G |
Reduced growth/survival signaling |
Frequently reported for anthraquinones (aloe-emodin/emodin/aloin) and some crude extracts; formulation is a major confounder. |
| 3 |
NF-κB inflammatory signaling |
↓ (often) (context-dependent) |
↓ (context-dependent) |
P/R |
Anti-inflammatory signaling shift |
Most relevant to supportive-care phenotypes (dermatitis/mucositis) and immune microenvironment modulation rather than direct tumor cytotoxicity. |
| 4 |
Immune activation by gel polysaccharides |
Indirect effects via immune context |
Macrophage/DC activation↑; cytokines↑ |
R/G |
Immunomodulation and tissue repair support |
Acemannan is the best-characterized polysaccharide; systemic anticancer translation remains uncertain, but local mucosal/skin benefit is plausible. |
| 5 |
ROS modulation |
↑ (high concentration only) or ↓ (antioxidant fractions) |
↓ (antioxidant fractions) or ↔ |
P/R |
Redox stress or scavenging |
Direction depends strongly on preparation: gel fractions are commonly framed as antioxidant; anthraquinone-rich fractions often act pro-oxidatively in cancer assays. |
| 6 |
NRF2 antioxidant-response axis |
↔ / ↑ (context-dependent) |
↑ (context-dependent) |
G |
Adaptive antioxidant signaling |
Not consistently “primary” for AV in oncology; include as secondary because redox-adaptation can modulate therapy response and inflammation. |
| 7 |
EMT, migration, invasion |
↓ (model-dependent) |
↔ |
G |
Reduced metastatic phenotypes |
Mostly preclinical; often co-reported with NF-κB/PI3K-AKT changes and MMP/EMT markers. |
| 8 |
Radiosensitization or Chemosensitization |
↔ (insufficient clinical proof) |
Radioprotection reported (context-dependent) |
R/G |
Supportive-care modulation vs sensitization |
Human studies more often evaluate symptom mitigation (dermatitis/mucositis) than tumor response; do not infer sensitization without direct tumor-outcome trials. |
| 9 |
Clinical Translation Constraint |
Preparation heterogeneity; polysaccharide PK limitations; anthraquinone-driven GI effects; safety signals for nondecolorized whole-leaf extracts; evidence base mostly supportive-care |
— |
Whole-leaf (nondecolorized) extracts are classified as possibly carcinogenic to humans (IARC 2B) and produced large-intestine tumors in rodent studies; “gel-only” and decolorized/low-anthraquinone products are not equivalent. |