Deguelin / Akt Cancer Research Results

Deg, Deguelin: Click to Expand ⟱
Features: Insect poisoning, anti-cancer
Deguelin is a natural compound of the flavonoid family of products isolated from several plant species, including Derris trifoliata Lour and Mundulea sericea (Leguminosae) (4)

Deguelin’s ability to modulate multiple signaling pathways—including PI3K/Akt, mTOR, NF-κB, HIF-1α, and MAPK
While preclinical studies have utilized dosages in the approximate range of 4–8 mg/kg in animal models, these figures are specific to the experimental conditions and species used in those studies.

Deguelin is a rotenoid (isoflavonoid-like botanical insecticide class) found in some Lonchocarpus / Derris species. In cancer literature it’s most often described as a mitochondrial Complex I inhibitor with downstream energy stress + survival pathway suppression (Akt/PI3K, NF-κB) and apoptosis/autophagy induction. A major caution is neurotoxicity signal: rotenoids (including deguelin) have been used in Parkinson’s disease animal models via Complex I inhibition.
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Active identity: Rotenoid (deguelin) — a potent mitochondrial Complex I inhibitor with downstream energy-stress signaling (AMPK/mTOR), survival pathway suppression (Akt, NF-κB), and apoptosis/autophagy induction in cancer models; higher caution category due to rotenoid neurotoxicity signals in animal models.



Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 Mitochondrial ETC Complex I inhibition (OXPHOS) Complex I ↓; ATP ↓; energetic stress ↑ (reported) Toxicity risk if exposure high/prolonged (mitochondrial inhibition) P, R Bioenergetic choke-point Deguelin is a rotenoid-class Complex I inhibitor; downstream effects often reflect energy stress + ROS/redox destabilization.
2 PI3K → AKT survival axis Akt signaling ↓ (reported; chemoprevention & tumor models) ↔ R, G Survival/growth suppression Deguelin is widely described as an Akt-pathway suppressor in cancer/chemoprevention literature.
3 AMPK → mTOR → survivin axis AMPK ↑; mTOR ↓; survivin ↓ (reported) ↔ R, G Energy-stress signaling → anti-growth Frequently presented as a mechanistic bridge between mitochondrial inhibition and reduced survival/proliferation programs.
4 NF-κB inflammatory / survival transcription IKK/IκB/NF-κB activity ↓ (reported) Inflammation tone ↓ (context) R, G Anti-inflammatory + anti-survival transcription Deguelin has been reported to suppress NF-κB signaling in multiple tumor systems.
5 Hsp90 client disruption (Akt, survivin, CDK4) (reported) Hsp90 client stability ↓; Akt/survivin/CDK4 ↓ (reported) ↔ R, G Multi-node pathway destabilization Some models report deguelin disrupts Hsp90-client interactions contributing to survival/proliferation collapse.
6 Intrinsic apoptosis (mitochondrial) ΔΨm ↓; cytochrome-c ↑; caspases ↑; cl-PARP ↑ (reported) ↔ / toxicity risk at higher exposure G Cell death execution Often downstream of energetic stress + survival pathway suppression.
7 Autophagy modulation Autophagy ↑ (reported; context-dependent; can be pro-death or adaptive) ↔ G Stress response / cell fate shift Autophagy is frequently reported alongside apoptosis; directionality and functional role vary by model.
8 Cell-cycle control Arrest ↑ (reported); cyclins/CDKs ↓ (context) ↔ G Cytostasis Often explained as downstream of Akt/mTOR and Hsp90-client disruption effects.
9 Angiogenesis / hypoxia programs (HIF-1α, VEGF) (reported) HIF-1α/VEGF outputs ↓ (reported in some models) ↔ R, G Anti-angiogenic support Anti-angiogenic effects are reported but are less “core” than the mitochondrial/Akt axes.
10 Safety constraint: rotenoid neurotoxicity signal — Parkinsonism-like syndrome reported in rat model with deguelin exposure — Translation constraint Deguelin (like rotenone) is a potent Complex I inhibitor; neurotoxicity signals exist in animal PD models, so long-term/high exposure should be treated as higher-risk than typical polyphenols.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (bioenergetic inhibition begins; early redox/kinase shifts)
  • R: 30 min–3 hr (AMPK/mTOR/NF-κB and stress pathway rewiring)
  • G: >3 hr (cell-cycle arrest, apoptosis/autophagy outcomes)
Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
1443- Deg,    Deguelin Action Involves c-Met and EGFR Signaling Pathways in Triple Negative Breast Cancer Cells
- vitro+vivo, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-435 - in-vitro, BC, BT549
EGFR↓, Akt↓, p‑ERK↓, NF-kB↓, p‑STAT3↓, survivin↓, Myc↓, TumCG↓, cMET↓,
1444- Deg,    Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer
- in-vitro, GC, MKN-28
Casp9↑, Casp3↑, Hif1a↓, VEGF↓, TumCCA↑, TumCG↓, DNAdam↑, p‑Akt↓,
1445- Deg,    Deguelin--an inhibitor to tumor lymphangiogenesis and lymphatic metastasis by downregulation of vascular endothelial cell growth factor-D in lung tumor model
- in-vivo, lymphoma, NA - in-vitro, lymphoma, NA
Akt↓, TumCP↓, TumCMig↓, VEGF↓, TumCG↓, OS↑,
1446- Deg,    Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells
- in-vitro, BC, 4T1
cMET↓, p‑ERK↓, p‑Akt↓, TumCMig↓, TumCG↓, Weight∅, *toxicity∅, Hif1a↓, TumMeta↓,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 2,   Casp3↑, 1,   Casp9↑, 1,   Myc↓, 1,   survivin↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 2,   p‑ERK↓, 2,   p‑STAT3↓, 1,   TumCG↓, 4,  

Migration ⓘ

TumCMig↓, 2,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 2,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   Weight∅, 1,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
4 Deguelin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:69  Target#:4  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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