Plumbagin / SHP1 Cancer Research Results

PLB, Plumbagin: Click to Expand ⟱
Features:
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naturally occurring naphthoquinone derivative.

–Plumbagin can undergo redox cycling to generate reactive oxygen species (ROS)
-apototosis, activation of caspases, modulation of Bax, Bcl‑2, loss of MMP.
-Cell cycle arrest in cancer cells, often at the G0/G1, or G2/M phases.
-May inhibit NF‑κB activation
– MAPK Pathways
– PI3K/Akt Pathway
-Downregulation of (VEGF) and matrix metalloproteinases (MMPs).

-Seems capable of raising ROS in normal and cancer cells (#2004)

-ic50 cancer cells 1-10uM, normal cells >10uM

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Oxidative stress (redox cycling) ↑ ROS Upstream cytotoxic trigger Plumbagin induces ROS; ROS generation is causally linked to cell death in cancer models (ref)
2 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Mitochondrial dysfunction Loss of mitochondrial membrane potential occurs during plumbagin-induced apoptotic progression (ref)
3 Intrinsic apoptosis (caspase cascade) ↑ caspase-dependent apoptosis Programmed cell death Plumbagin triggers apoptosis in leukemia and solid tumor cells; antioxidant rescue attenuates killing (ref)
4 NF-κB signaling ↓ NF-κB activation Reduced pro-survival / inflammatory transcription Demonstrates plumbagin suppresses NF-κB signaling in tumor/immune contexts (direction explicitly shown) (ref)
5 STAT3 signaling ↓ STAT3 phosphorylation Reduced survival & proliferation signaling Plumbagin suppresses constitutive and inducible STAT3 phosphorylation in cancer cells (ref)
6 PI3K–AKT–mTOR signaling ↓ PI3K/AKT/mTOR activity Survival pathway suppression Plumbagin inhibits PI3K/AKT/mTOR signaling in cancer cells with linked apoptosis/autophagy outcomes (ref)
7 Autophagy program ↑ autophagy Stress response (context-dependent role) Plumbagin induces autophagy alongside apoptosis; pathway involvement (p38, PI3K/AKT/mTOR) is demonstrated (ref)
8 Stress MAPK (p38 MAPK) ↑ p38 activation Stress signaling amplification p38 MAPK activation is implicated in plumbagin-driven apoptosis/autophagy signaling in cancer cells (ref)
9 Cell cycle control ↑ G2/M (or S–G2/M) arrest Proliferation blockade Plumbagin induces checkpoint arrest with changes in cyclins/CDKs consistent with growth inhibition (ref)
10 Death receptor axis (TRAIL receptors DR4/DR5) ↑ DR4/DR5 expression Sensitizes to TRAIL-mediated killing Plumbagin increases DR4/DR5 and enhances TRAIL killing; NAC blocks both ROS and receptor upregulation (ref)
11 EMT / invasion programs ↓ EMT (anti-invasive) Reduced metastasis-related phenotype Plumbagin suppresses epithelial–mesenchymal transition and stemness-related markers in cancer cells (ref)
12 Angiogenesis signaling (VEGFR2/VEGF-driven endothelial responses) ↓ angiogenesis signaling / function Anti-angiogenic effect Plumbagin inhibits tumor angiogenesis via interference with VEGFR2-mediated signaling in endothelial/tumor models (ref)


SHP1, Src Homology region 2 domain-containing Phosphatase-1: Click to Expand ⟱
Source:
Type:
SHP1 is a non-receptor protein tyrosine phosphatase primarily encoded by the gene PTPN6.
Immune Checkpoint Brake, Tumor Suppressor Signaling, and Immune Evasion

– In blood cancers such as leukemia and lymphoma, altered SHP1 expression (often downregulation) is frequently observed.
– Downregulation or loss of SHP1 is often associated with more aggressive disease phenotypes and poorer prognosis.
Direction of Regulation in Cancer 
Two distinct, context-specific directions:
A. Tumor Cells (especially hematologic malignancies): DOWNREGULATED
-Frequently silenced epigenetically (promoter methylation)
-Rarely mutated; loss is regulatory
-Results in unchecked growth and survival signaling

B. Immune Cells within the Tumor Microenvironment: FUNCTIONALLY UPREGULATED
-Actively recruited by inhibitory receptors
-Suppresses T-cell, NK-cell, and myeloid anti-tumor responses
-Promotes immune evasion

This duality is critical to interpret SHP1 correctly.

When SHP1 is lost in tumor cells:
-JAK–STAT signaling becomes hyperactive
-Growth and survival pathways escape negative feedback
-Cells gain a proliferative and survival advantage


Scientific Papers found: Click to Expand⟱
5160- PLB,  VitK3,    Plumbagin, Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization
- in-vitro, Melanoma, U266
STAT3↓, cSrc↓, JAK1↓, JAK2↓, SHP1↑, cycD1/CCND1↓, Bcl-xL↓, VEGF↓, Casp3↑, cl‑PARP↑, TumCCA↑, ChemoSen↑,

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 ⓘ

Bcl-xL↓, 1,   Casp3↑, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

SHP1↑, 1,   STAT3↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

JAK1↓, 1,   JAK2↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  
Total Targets: 12

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: SHP1, Src Homology region 2 domain-containing Phosphatase-1
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#:299  Target#:1331  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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