Gambogic Acid / cycD1/CCND1 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)


cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
5150- GamB,    Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway
- in-vitro, CLL, KBM-5 - in-vitro, Nor, HEK293
Apoptosis↑, ChemoSen↑, IAP1↓, IAP2↓, Bcl-2↓, Bcl-xL↓, TRAF1↓, cycD1/CCND1↓, cMyc↓, COX2↓, MMP9↓, angioG↓, VEGF↓, NF-kB↓, eff↓,

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:


Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   IAP1↓, 1,   IAP2↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Migration ⓘ

MMP9↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 1,   TRAF1↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,  
Total Targets: 15

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
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#:73  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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