Plumbagin / TrxR 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)


TrxR, Thioredoxin Reductase: Click to Expand ⟱
Source:
Type:
TrxR is an enzyme that reduces Trx, allowing it to perform its reducing functions. It has been shown to have a role in cancer cell metabolism and survival.
TrxR is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer.

- Part of the thioredoxin system, which regulates reactive oxygen species (ROS).
- TrxR is a major antioxidant systems that maintains the intracellular redox homeostasis.
- Inhibition causes an increase in ROS.
- TrxR is often upregulated in cancer cells to help manage increased oxidative stress, it is seen as a potential therapeutic target. Inhibiting TrxR may result in increased ROS in cancer cells, pushing them toward apoptosis.
- TrxR is a selenoprotein—meaning it incorporates the trace element selenium in the form of the amino acid selenocysteine.

TrxR inhibitors:
-Piperlongumine
-Withania somnifera (Ashwagandha)
-Parthenolide
-EGCG
-Curcumin
-Myricetin
-Gambogic Acid
Scientific Papers found: Click to Expand⟱
2651- PLB,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, TrxR↓, GSR↓, ER Stress↓, TumCCA↑, MMP↓, NF-kB↓, PI3K↓, Akt↓, mTOR↓, MKP1↓, MKP2↓, 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:


Redox & Oxidative Stress ⓘ

GSR↓, 1,   ROS↑, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   MKP1↓, 1,   MKP2↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,   PI3K↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TrxR, Thioredoxin Reductase
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#:825  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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