Deguelin / PI3K/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)
PI3K/Akt, PI3K/Akt signaling: Click to Expand ⟱
Source: HalifaxProj(inhibit) TCGA
Type:
The PI3K/Akt signaling pathway plays a crucial role in various cellular processes, including growth, proliferation, survival, and metabolism.
Pathway Components:
Phosphoinositide 3-kinases (PI3Ks): A family of enzymes that phosphorylate the inositol ring of phosphatidylinositol, leading to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3).
Akt (Protein Kinase B): A serine/threonine kinase that is activated by PIP3. Once activated, Akt phosphorylates various substrates involved in cell survival and growth.
Overactivation can lead to uncontrolled cell growth.
Angiogenesis: Akt can promote the expression of pro-angiogenic factors, facilitating the formation of new blood vessels to supply tumors with nutrients and oxygen.
Scientific Papers found: Click to Expand⟱
19- Deg,    Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway
- in-vitro, PC, Bxpc-3 - in-vitro, PC, PANC1
HH↓, Gli1↓, PTCH1↓, Sufu↓, MMP2↓, MMP9↓, PI3K/Akt↓, HIF-1↓, VEGF↓, IKKα↓, NF-kB↓, EMT↓, AMPK↑, mTOR↓, survivin↓, TumCG↓, Apoptosis↑, TumCMig↓, TumCI↓,
1442- Deg,    Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention
- Review, Var, NA
PI3K/Akt↓, IKKα↓, AMP↓, mTOR↓, survivin↓, NF-kB↓, Apoptosis↑, TumCCA↑, toxicity↓, HSP90↓, Casp↑, TumCG↓, p27↑, cycE/CCNE↓, angioG↓, Hif1a↓, VEGF↓, *toxicity↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

AMP↓, 1,   AMPK↑, 1,   PI3K/Akt↓, 2,  

Cell Death ⓘ

Apoptosis↑, 2,   Casp↑, 1,   p27↑, 1,   survivin↓, 2,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

Cell Cycle & Senescence ⓘ

cycE/CCNE↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   Gli1↓, 1,   HH↓, 1,   mTOR↓, 2,   PTCH1↓, 1,   Sufu↓, 1,   TumCG↓, 2,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumCI↓, 1,   TumCMig↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   HIF-1↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

IKKα↓, 2,   NF-kB↓, 2,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 28

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity↑, 1,  
Total Targets: 1

Scientific Paper Hit Count for: PI3K/Akt, PI3K/Akt signaling
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#:253  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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