Gambogic Acid / Cyt‑c 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)


Cyt‑c, cyt-c Release into Cytosol: Click to Expand ⟱
Source:
Type:
Cytochrome c
** The term "release of cytochrome c" ** an increase in level for the cytosol.
Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis.

The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.
In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.
Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.
Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.
The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.

On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.
On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.
Overexpressed in Breast, Lung, Colon, and Prostrate.
Underexpressed in Ovarian, and Pancreatic.
Scientific Papers found: Click to Expand⟱
5152- GamB,    Gambogic Acid as a Candidate for Cancer Therapy: A Review
- Review, Var, NA
AntiCan↑, Apoptosis↑, TumAuto↑, TumCCA↑, TumCI↓, TumMeta↓, angioG↓, eff↑, NF-kB↓, P53↑, P21↑, MDM2↓, HSP90↓, Bcl-2↓, Cyt‑c↑, Casp↑, MMP↓, Casp3↑, Casp9↑, cl‑PARP↑, Bax:Bcl2↑, ROS↑, SIRT1↓, TrxR1↓, Fas↓, FasL↑, FADD↑, APAF1↑, DNAdam↑, NF-kB↓, STAT3↓, MAPK↓, cFos↓, EGFR↓, Akt↓, mTOR↓, AMPK↑, TumCCA↑, ChemoSen↑, P-gp↓, survivin↓,
1969- GamB,    Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells
- in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
AntiTum↑, TumCI↓, Apoptosis↑, ROS↑, Cyt‑c↑, Akt↓, mTOR↓, TumCG↓, TumMeta↓,
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↑,
1959- GamB,    Gambogic acid induces GSDME dependent pyroptotic signaling pathway via ROS/P53/Mitochondria/Caspase-3 in ovarian cancer cells
- in-vitro, Ovarian, NA - in-vivo, NA, NA
AntiCan↑, Pyro↑, tumCV?, CellMemb↓, cl‑Casp3↑, GSDME-N↑, ROS?, p‑P53↑, eff↓, MMP↓, Bcl-2↓, BAX↑, mtDam↑, Cyt‑c↑, TumCG↓, CD4+↑, CD8+↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS?, 1,   ROS↑, 3,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 2,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Casp↑, 1,   Casp3↑, 1,   cl‑Casp3↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 4,   FADD↑, 1,   Fas↓, 1,   FasL↑, 1,   GSDME-N↑, 1,   MAPK↓, 1,   MDM2↓, 1,   Pyro↑, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

tumCV?, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   p‑P53↑, 1,   cl‑PARP↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   mTOR↓, 2,   STAT3↓, 1,   TumCG↓, 2,  

Migration ⓘ

TumCI↓, 2,   TumMeta↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,  

Barriers & Transport ⓘ

CellMemb↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD4+↑, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 58

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Cyt‑c, cyt-c Release into Cytosol
4 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#:77  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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