Gambogic Acid / AMPK 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)

AMPK, adenosine monophosphate-activated protein kinase: Click to Expand ⟱

Source:

Type:

AMPK: guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways.

-Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation.

AMPK activators:
-metformin or AICAR
-Resveratrol: activate AMPK indirectly
-Berberine
-Quercetin: may stimulate AMPK
-EGCG: thought to activate AMPK
-Curcumin: may activate AMPK

-Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models.
-Alpha-Lipoic Acid (ALA): associated with AMPK activation

Scientific Papers found: Click to Expand⟱

5152-

GamB,

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Review,

Var,

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↓,

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:

Functional Outcomes ⓘ

AntiCan↑, 1,
Total Targets: 40

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: AMPK, adenosine monophosphate-activated protein kinase

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#:9  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Gambogic Acid / AMPK Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

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