Gambogic Acid / Casp8 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)


Casp8, CASP8, caspase 8, apoptosis-related cysteine peptidase: Click to Expand ⟱
Source: CGL-Driver Genes
Type: TSG
Caspase-8 is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer.
Caspase-8 (Casp8) acts as an initiator in cell apoptosis signaling. However, the role of Casp8 in tuning the tumor immune microenvironment remains controversial due to the complicated crosstalk between immune-tolerogenic apoptotic cell death and immunogenic cell death cascades.
Scientific Papers found: Click to Expand⟱
5149- GamB,    Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cells
- in-vitro, lymphoma, JeKo-1
TumCG↓, Apoptosis↑, selectivity↑, MMP↓, Casp3↑, Casp9↑, Casp8↑, Bax:Bcl2↑,
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↑,
1967- GamB,    Gambogic acid induces apoptotic cell death in T98G glioma cells
- in-vitro, GBM, T98G
BAX↑, AIF↑, Cyt‑c↑, cl‑Casp3↑, cl‑Casp8↑, cl‑Casp9↑, cl‑PARP↓, Bcl-2↓, ROS↑,

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 ⓘ

ROS↑, 2,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAD↓, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 2,   BID↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   cFLIP↓, 1,   Cyt‑c↑, 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,   cl‑PARP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 2,  

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,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 1,   eff↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 50

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp8, CASP8, caspase 8, apoptosis-related cysteine peptidase
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#:44  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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