Sanguinarine / PI3K Cancer Research Results

SANG, Sanguinarine: Click to Expand ⟱
Features:

Sanguinarine (SANG) — a benzophenanthridine alkaloid isolated primarily from Sanguinaria canadensis (bloodroot) and other Papaveraceae species. Potent redox-active, DNA-intercalating phytochemical studied extensively in preclinical oncology.

Primary mechanisms (conceptual rank):
1) ROS generation → mitochondrial apoptosis
2) NF-κB / STAT3 inhibition (anti-survival signaling)
3) Cell-cycle arrest (G0/G1 or G2/M depending on model)
4) MAPK modulation (JNK activation; ERK suppression context-dependent)
5) Epigenetic/DNA interaction effects

Bioavailability / PK relevance: Limited human PK data; rapid reactivity and protein binding likely restrict systemic exposure. Toxicity (oral mucosal injury, cytotoxicity) limits therapeutic window.

In-vitro vs oral exposure: Many anti-cancer effects occur at micromolar concentrations unlikely achievable systemically via safe oral dosing (qualifier: high concentration only for direct cytotoxicity).

Clinical evidence status: Preclinical oncology only; no validated RCT cancer indication. Safety concerns limit development.

Extracted from bloodroot plant from whose scientific name, Sanguinaria canadensis, its name is derived; the Mexican prickly poppy; Chelidonium majus; and Macleaya cordata.

Sanguinarine — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS / Mitochondrial redox stress ↑ (primary; dose-dependent) ↑ (high concentration only) P/R Oxidative stress → apoptosis Central mechanism; rapid ROS generation drives mitochondrial membrane depolarization and cytochrome c release.
2 Intrinsic apoptosis (Bax↑, Bcl-2↓, caspases) ↑ ↑ (high concentration only) R/G Programmed cell death Often ROS-dependent; cancer cells show greater susceptibility due to higher basal oxidative stress.
3 NF-κB signaling ↓ ↓ (context-dependent) R/G Reduced pro-survival transcription Suppresses inflammatory and anti-apoptotic gene expression; contributes to anti-proliferative effect.
4 STAT3 axis ↓ ↔ R/G Reduced survival signaling STAT3 inhibition reported in multiple tumor models; linked to decreased proliferation and invasion.
5 MAPK (JNK↑ / ERK↓ context-dependent) ↑ JNK; ↓ ERK ↔ / ↑ stress (high dose) P/R Stress-activated apoptosis signaling JNK activation promotes apoptosis; ERK suppression reduces proliferation.
6 Cell Cycle (Cyclin D1, CDK regulation) ↓ proliferation ↔ G G0/G1 or G2/M arrest Checkpoint enforcement varies by tumor type and dose.
7 NRF2 axis ↓ (overwhelmed by ROS; context-dependent) ↑ (adaptive; low dose) R/G Redox defense modulation Low dose may activate adaptive NRF2; higher doses override antioxidant defenses in cancer cells.
8 Ca²⁺ / ER stress ↑ (stress-dependent) ↑ (high concentration only) P/R ER-mitochondrial stress coupling Calcium dysregulation contributes to apoptosis cascade.
9 Ferroptosis ↑ (lipid ROS-linked; investigational) ↔ R/G Lipid peroxidation stress ROS-driven lipid damage suggests ferroptosis overlap but not primary established mechanism.
10 HIF-1α ↓ (model-dependent) ↔ G Reduced hypoxia adaptation Reported suppression in some tumor contexts.
11 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — Toxicity + limited PK data Oral toxicity and narrow therapeutic index limit systemic development.

TSF legend:
P: 0–30 min (primary redox interactions)
R: 30 min–3 hr (acute stress signaling)
G: >3 hr (gene-regulatory / phenotype outcomes)
PI3K, Phosphatidylinositide-3-Kinases: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-CS
Type:
Phosphatidylinositol 3-kinase (PtdIns3K or PI3K) is a family of enzymes that play a crucial role in cell signaling pathways, particularly in the regulation of cell growth, survival, and metabolism. The PI3K pathway is one of the most frequently altered pathways in human cancer. Inhibition of the PI3K pathway has been explored as a therapeutic strategy for cancer treatment. Several PI3K inhibitors have been developed and are currently being tested in clinical trials. These inhibitors can target specific components of the pathway, such as PI3K, AKT, or mTOR.

Class I phosphoinositide 3-kinase (PI3K)
Class III PtdIns3K
In contrast to the class III PtdIns3K as a positive regulator of autophagy, class I PI3K-AKT signaling has an opposing effect on the initiation of autophagy.

PI3K inhibitors include:
-Idelalisib , Copanlisib, Alpelisib
-LY294002?
-Wortmannin: potent PI3K inhibitor, has some associated toxicity.
-Quercetin:
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
Scientific Papers found: Click to Expand⟱
1134- SANG,    Sanguinarine inhibits epithelial–mesenchymal transition via targeting HIF-1α/TGF-β feed-forward loop in hepatocellular carcinoma
- in-vitro, HCC, HepG2 - in-vitro, HCC, Hep3B - in-vitro, HCC, HUH7
Hif1a↓, EMT↓, Snail↓, PI3K↓, Akt↓, SMAD2↓, SMAD3↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Akt↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   PI3K↓, 1,  

Migration ⓘ

SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  
Total Targets: 7

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: PI3K, Phosphatidylinositide-3-Kinases
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#:147  Target#:252  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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