Gambogic Acid / MMP 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)


MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱
Source:
Type:
Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.


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↓,
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↑,
1971- GamB,    Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis
- in-vitro, Nor, MCF10 - in-vitro, BC, MDA-MB-435 - in-vitro, BC, MDA-MB-468 - in-vivo, NA, NA
Paraptosis↑, ER Stress↑, MMP↓, eff↓, selectivity↑, p‑ERK↑, p‑JNK↑, eff↓,
1962- GamB,  HCQ,    Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species
- in-vitro, PC, NA
LC3II↑, Beclin-1↑, p62↓, MMP↓, ROS↑, TumAuto↑, eff↑,
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+↑,
1957- GamB,    Nanoscale Features of Gambogic Acid Induced ROS-Dependent Apoptosis in Esophageal Cancer Cells Imaged by Atomic Force Microscopy
- in-vitro, ESCC, EC9706
AntiCan↑, toxicity↓, TumCP↓, Apoptosis↑, TumCCA↑, MMP↓, ROS↑, eff↓, RadioS↑,
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 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   ROS?, 1,   ROS↑, 5,   Trx↓, 1,   TrxR↓, 3,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 8,   mtDam↑, 1,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   NADPH↓, 1,   SIRT1↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 4,   BAD↓, 1,   BAX↑, 2,   Bax:Bcl2↑, 2,   Bcl-2↓, 3,   BID↓, 1,   Casp↑, 2,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 2,   Casp9↑, 3,   cFLIP↓, 1,   Cyt‑c↑, 2,   FADD↑, 1,   Fas↓, 1,   FasL↑, 1,   Ferroptosis↑, 1,   GSDME-N↑, 1,   hTERT/TERT↓, 1,   p‑JNK↑, 1,   MAPK↓, 1,   MDM2↓, 1,   Myc↓, 1,   Paraptosis↑, 1,   Pyro↑, 1,   survivin↓, 2,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

FOXD3↑, 1,  

Transcription & Epigenetics ⓘ

tumCV?, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   HSP90↓, 2,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   p‑P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   ERK↓, 1,   p‑ERK↑, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 2,   TumCG↓, 3,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   CellMemb↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD4+↑, 1,   NF-kB↓, 3,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 3,   Dose∅, 1,   eff↓, 5,   eff↑, 4,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

AntiCan↑, 4,   toxicity↓, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 93

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential
8 Gambogic Acid
1 hydroxychloroquine
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#:197  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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