Gambogic Acid / p66Shc 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)

p66Shc, p66Shc: Click to Expand ⟱

Source:

Type:

p66Shc is one of three isoforms encoded by the ShcA gene and is well known for its roles in oxidative stress response, apoptosis, and cellular metabolism.

• Some studies have revealed that altered p66Shc expression is associated with changes in oxidative stress signaling.
• Elevated p66Shc activity in certain contexts has been linked to enhanced reactive oxygen species (ROS) production, which may promote tumor progression.
• However, the exact relationship is complex; in some research, higher p66Shc levels have been associated with increased cancer cell apoptosis and a better prognosis, while in other studies a pro-oxidative environment may favor tumor aggressiveness.

Scientific Papers found: Click to Expand⟱

1956-

GamB,

Gambogic Acid Inhibits Malignant Melanoma Cell Proliferation Through Mitochondrial p66shc/ROS-p53/Bax-Mediated Apoptosis

in-vitro,

Melanoma,

A375

1-10 μg/ml

tumCV↓, Apoptosis↑, ROS↑, p66Shc↑,

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:

Redox & Oxidative Stress ⓘ

p66Shc↑, 1, ROS↑, 1,

Cell Death ⓘ

Apoptosis↑, 1,

Transcription & Epigenetics ⓘ

tumCV↓, 1,
Total Targets: 4

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: p66Shc, p66Shc

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