Database Query Results : Sanguinarine, ,

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)
Scientific Papers found: Click to Expand⟱
1945- PL,  SANG,    The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer
- in-vitro, Lung, A549
toxicity∅, Apoptosis↑, TumMeta↓, ROS↑, TumCCA↑,
1090- SANG,    Sanguinarine inhibits invasiveness and the MMP-9 and COX-2 expression in TPA-induced breast cancer cells by inducing HO-1 expression.
- in-vitro, BC, MCF-7
MMP9↓, COX2↓, PGE2↓, NF-kB↓, AP-1↓, p‑Akt↓, p‑ERK↓, HO-1↑,
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↓,
1208- SANG,    Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single-stranded DNA-binding protein 1 (SSBP1) promoter region
- in-vitro, OS, NA
SSBP1↑, mtDam↑, Apoptosis↑, JAK↓, STAT3↓, PI3k/Akt/mTOR↓, ROS↑, MMP↓,
1209- SANG,    Sanguinarine is a novel VEGF inhibitor involved in the suppression of angiogenesis and cell migration
- in-vitro, Lung, A549
VEGF↓, TumCMig↓, Akt↓, p38↓,
1210- SANG,    Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1α pathways in breast cancer
- in-vitro, BC, NA
EphB4↓, Hif1a↓, STAT3↓, MAPK↓, ERK↓,
1307- SANG,    Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway
- in-vitro, CRC, HT-29
Apoptosis↑, BAX↑, Bcl-2↓, Casp3↑, Casp9↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 1,   SSBP1↑, 1,  

Core Metabolism/Glycolysis ⓘ

PI3k/Akt/mTOR↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   MAPK↓, 1,   p38↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   p‑ERK↓, 1,   PI3K↓, 1,   STAT3↓, 2,  

Migration ⓘ

AP-1↓, 1,   EphB4↓, 1,   MMP9↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 2,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   JAK↓, 1,   NF-kB↓, 1,   PGE2↓, 1,  

Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 36

Pathway results for Effect on Normal Cells:


Total Targets: 0

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#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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