Gambogic Acid / TrxR Cancer Research Results

GamB, Gambogic Acid: Click to Expand ⟱
Features:
Gambogic acid is a naturally occurring xanthonoid extracted from the resin of trees belonging to the Garcinia genus—most notably, Garcinia hanburyi. This tree is native to regions in Southeast Asia, particularly found in areas of China, India, and neighboring countries.
Gambogic acid (GA; C38H44O8, MW: 628.76), a polyprenylated xanthone and a widely used coloring agent, is the main active ingredient of gamboges secreted from the Garcinia hanburyi tree ([3, 4], which mainly grows in Southeast Asia.
GA has been approved by the Chinese FDA for the treatment of solid cancers in Phase II clinical trials.

Pathways:
-evidence suggesting that it can inhibit thioredoxin reductase (TrxR).
-can indeed lead to an increase in reactive oxygen species (ROS) levels
-Gambogic acid can trigger mitochondrial dysfunction, leading to cytochrome c release
-influences death receptors
-Inhibition of NF-κB Signaling
-Inhibition of VEGF Pathway
-Cell Cycle Arrest:
-p53 Activation
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Thioredoxin / Thioredoxin reductase (Trx / TrxR) ↓ Trx / TrxR activity Redox buffering collapse Primary molecular target; covalent cysteine interaction drives loss of antioxidant capacity (ref)
2 ROS accumulation ↑ ROS Oxidative stress overload Immediate consequence of Trx/TrxR inhibition; upstream of mitochondrial damage (ref)
3 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Mitochondrial dysfunction GA reduces mitochondrial membrane potential prior to execution-phase death (ref)
4 Intrinsic apoptosis / pyroptosis (caspase-3, GSDME) ↑ programmed cell death Execution-phase killing Mitochondrial apoptosis and caspase-3/GSDME-dependent pyroptosis reported (ref)
5 NF-κB signaling ↓ NF-κB activation Reduced pro-survival transcription Redox-sensitive suppression of NF-κB nuclear activity and target genes (ref)
6 PI3K–AKT survival signaling ↓ AKT phosphorylation Survival pathway collapse Downstream of oxidative stress and chaperone disruption (ref)
7 HSP90 chaperone function ↓ client stabilization Oncoprotein destabilization GA disrupts HSP90–client interactions affecting AKT, HER2, etc. (ref)
8 ER stress / UPR ↑ ER stress signaling Proteotoxic stress Secondary ER stress response following redox and mitochondrial disruption (ref)
9 Cell cycle regulation ↑ cell-cycle arrest Proliferation blockade Checkpoint activation downstream of stress signaling (ref)
10 Autophagy (stress-induced) ↑ autophagy Adaptive or pro-death response Autophagy induction reported; role varies by context (ref)
11 Angiogenesis signaling (VEGF) ↓ VEGF expression Anti-angiogenic effect Suppression of pro-angiogenic transcription observed (ref)
12 Tumor growth in vivo ↓ tumor volume Integrated outcome Xenograft models show significant tumor growth inhibition (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⟱
5148- GamB,    Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics
- Review, Var, NA
AntiCan↑, angioG↓, ChemoSen↑, RadioS↑, VEGF↓, MMP2↓, MMP9↓, Telomerase↓, TrxR↓, ERK↓, HSP90↓, ROS↑, SIRT1↑, survivin↓, cFLIP↓, Casp3↑, Casp8↑, Casp9↑, BAD↓, BID↓, Bcl-2↓, BAX↑, STAT3↓, hTERT/TERT↓, NF-kB↓, Myc↓, Hif1a↓, FOXD3↑, BioAv↓, BioAv↑, P53↑, eff↓, OCR↓, MMP↓, PI3K↓, Akt↓, BBB↑, TumCG↓, TumMeta↓, BioAv↑,
1954- GamB,    Gambogic acid induces apoptosis in hepatocellular carcinoma SMMC-7721 cells by targeting cytosolic thioredoxin reductase
- in-vitro, HCC, SMMC-7721 cell
AntiTum↑, TrxR↓, TrxR1↓, ROS↑, Apoptosis↑, Dose∅, Dose?,
1955- GamB,    Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancer
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
ROS↑, Apoptosis↑, Ferroptosis↑, Trx↓, eff↑, TrxR↓, Dose∅, MMP↓, eff↑, Casp↑, NADPH↓, TrxR↓, ChemoSen↑, AR↓,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   ROS↑, 3,   Trx↓, 1,   TrxR↓, 4,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAD↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   BID↓, 1,   Casp↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   cFLIP↓, 1,   Ferroptosis↑, 1,   hTERT/TERT↓, 1,   Myc↓, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

FOXD3↑, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 2,   Dose?, 1,   Dose∅, 2,   eff↓, 1,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   hTERT/TERT↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,  
Total Targets: 54

Pathway results for Effect on Normal Cells:


Total Targets: 0

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

 

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