tbResList Print — GamB Gambogic Acid

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GamB Gambogic Acid
Description: <b>Gambogic acid</b> 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.<br>
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. <br>
GA has been approved by the Chinese FDA for the treatment of solid cancers in Phase II clinical trials.<br>
<br>
Pathways:<br>
-evidence suggesting that it can inhibit thioredoxin reductase (TrxR).<br>
-can indeed lead to an increase in reactive oxygen species (ROS) levels<br>
-Gambogic acid can trigger mitochondrial dysfunction, leading to cytochrome c release<br>
-influences death receptors<br>
-Inhibition of NF-κB Signaling<br>
-Inhibition of VEGF Pathway<br>
-Cell Cycle Arrest:<br>
-p53 Activation<br>



<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>

<tr>
<td>1</td>
<td>Thioredoxin / Thioredoxin reductase (Trx / TrxR)</td>
<td>↓ Trx / TrxR activity</td>
<td>Redox buffering collapse</td>
<td>Primary molecular target; covalent cysteine interaction drives loss of antioxidant capacity</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5652772/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>ROS accumulation</td>
<td>↑ ROS</td>
<td>Oxidative stress overload</td>
<td>Immediate consequence of Trx/TrxR inhibition; upstream of mitochondrial damage</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7484097/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓ ΔΨm</td>
<td>Mitochondrial dysfunction</td>
<td>GA reduces mitochondrial membrane potential prior to execution-phase death</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3626980/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>Intrinsic apoptosis / pyroptosis (caspase-3, GSDME)</td>
<td>↑ programmed cell death</td>
<td>Execution-phase killing</td>
<td>Mitochondrial apoptosis and caspase-3/GSDME-dependent pyroptosis reported</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3626980/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB activation</td>
<td>Reduced pro-survival transcription</td>
<td>Redox-sensitive suppression of NF-κB nuclear activity and target genes</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2077305/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>PI3K–AKT survival signaling</td>
<td>↓ AKT phosphorylation</td>
<td>Survival pathway collapse</td>
<td>Downstream of oxidative stress and chaperone disruption</td>
<td><a href="https://www.jcancer.org/v11p5568.htm" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>HSP90 chaperone function</td>
<td>↓ client stabilization</td>
<td>Oncoprotein destabilization</td>
<td>GA disrupts HSP90–client interactions affecting AKT, HER2, etc.</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/18077578/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>ER stress / UPR</td>
<td>↑ ER stress signaling</td>
<td>Proteotoxic stress</td>
<td>Secondary ER stress response following redox and mitochondrial disruption</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/31138775/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>Cell cycle regulation</td>
<td>↑ cell-cycle arrest</td>
<td>Proliferation blockade</td>
<td>Checkpoint activation downstream of stress signaling</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7764553/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>Autophagy (stress-induced)</td>
<td>↑ autophagy</td>
<td>Adaptive or pro-death response</td>
<td>Autophagy induction reported; role varies by context</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7764553/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>↓ VEGF expression</td>
<td>Anti-angiogenic effect</td>
<td>Suppression of pro-angiogenic transcription observed</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2077305/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>Tumor growth in vivo</td>
<td>↓ tumor volume</td>
<td>Integrated outcome</td>
<td>Xenograft models show significant tumor growth inhibition</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3626980/" target="_blank">(ref)</a></td>
</tr>
</table>

Pathway results for Effect on Cancer / Diseased Cells

Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   Mich↑, 1,   p66Shc↑, 1,   ROS↑, 20,   ROS?, 1,   Trx↓, 2,   Trx1↓, 1,   Trx2↓, 1,   TrxR↓, 4,   TrxR1↓, 2,  

Metal & Cofactor Biology ⓘ

TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 8,   mtDam↑, 1,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

6PGD↓, 2,   AMPK↑, 1,   cMyc↓, 1,   NADPH↓, 1,   PPP↓, 2,   SIRT1↓, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   APAF1↑, 1,   Apoptosis↑, 11,   BAD↓, 1,   BAX↑, 4,   Bax:Bcl2↑, 2,   Bcl-2↓, 6,   Bcl-xL↓, 1,   BID↓, 1,   Casp↑, 3,   Casp12↑, 1,   cl‑Casp3↑, 3,   Casp3↑, 4,   cl‑Casp8↑, 1,   Casp8↑, 2,   cl‑Casp9↑, 2,   Casp9↑, 3,   cFLIP↓, 1,   Cyt‑c↑, 4,   FADD↑, 1,   Fas↓, 1,   FasL↑, 1,   Ferroptosis↑, 1,   GSDME-N↑, 1,   hTERT/TERT↓, 1,   IAP1↓, 1,   IAP2↓, 1,   JNK↑, 2,   p‑JNK↑, 1,   MAPK↓, 1,   MDM2↓, 1,   Myc↓, 1,   p38↑, 1,   Paraptosis↑, 1,   Proteasome↓, 1,   Pyro↑, 1,   survivin↓, 3,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

FOXD3↑, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   tumCV↓, 2,   tumCV?, 1,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↑, 1,   ER Stress↑, 5,   GRP78/BiP↑, 1,   HSP90↓, 2,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   p‑P53↑, 1,   P53↑, 2,   cl‑PARP↑, 2,   cl‑PARP↓, 1,   PARP↑, 1,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   p‑ERK↑, 1,   ERK↓, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   PI3K↓, 2,   PTEN↑, 1,   STAT3↓, 2,   TumCG↓, 7,  

Migration ⓘ

MMP2↓, 2,   MMP9↓, 3,   TumCI↓, 3,   TumCMig↓, 1,   TumCP↓, 4,   TumMeta↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Barriers & Transport ⓘ

BBB↑, 1,   CellMemb↓, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

CD4+↑, 1,   COX2↓, 1,   NF-kB↓, 4,   TRAF1↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 7,   Dose∅, 2,   Dose?, 1,   eff↑, 11,   eff↓, 9,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   EZH2↓, 1,   hTERT/TERT↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 6,   AntiTum↑, 2,   toxicity↓, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 131

Pathway results for Effect on Normal Cells

Total Targets: 0

Research papers

Year Title Authors PMID Link Flag
2017Naturally occurring anti-cancer agents targeting EZH2Fahimeh Shahabipour—https://www.sciencedirect.com/science/article/abs/pii/S03043835173018420
2025Gambogic acid induces GSDME dependent pyroptotic signaling pathway via ROS/P53/Mitochondria/Caspase-3 in ovarian cancer cellsDanya Zhang39643123https://pubmed.ncbi.nlm.nih.gov/39643123/0
2024Gambogic acid exhibits promising anticancer activity by inhibiting the pentose phosphate pathway in lung cancer mouse modelQianyu Zhang38692076https://pubmed.ncbi.nlm.nih.gov/38692076/0
2023Gambogenic acid induces apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress via JNK pathway in prostate cancer cellsJianjian Wu36086867https://pubmed.ncbi.nlm.nih.gov/36086867/0
2023Gambogenic acid induces apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress via JNK pathway in prostate cancer cellsJianjian Wu36086867https://pubmed.ncbi.nlm.nih.gov/36086867/0
2022Nanoscale Features of Gambogic Acid Induced ROS-Dependent Apoptosis in Esophageal Cancer Cells Imaged by Atomic Force MicroscopyJianxin LiuPMC9337977https://pmc.ncbi.nlm.nih.gov/articles/PMC9337977/0
2022Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cellsYinhua Zhu35876000https://pubmed.ncbi.nlm.nih.gov/35876000/0
2020Gambogic Acid as a Candidate for Cancer Therapy: A ReviewYuling LiuPMC7764553https://pmc.ncbi.nlm.nih.gov/articles/PMC7764553/0
2020Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathwayJiarui Yu—https://www.jcancer.org/v11p5568.htm0
2020Gambogic acid: A shining natural compound to nanomedicine for cancer therapeuticsElham HatamiPMC7484097https://pmc.ncbi.nlm.nih.gov/articles/PMC7484097/0
2019Gambogic Acid Shows Anti-Proliferative Effects on Non-Small Cell Lung Cancer (NSCLC) Cells by Activating Reactive Oxygen Species (ROS)-Induced Endoplasmic Reticulum (ER) Stress-Mediated ApoptosisMinghua ZhuPMC6559008https://pmc.ncbi.nlm.nih.gov/articles/PMC6559008/0
2019Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasisMin Ji SeoPMC6385239https://pmc.ncbi.nlm.nih.gov/articles/PMC6385239/0
2019Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen speciesHongcheng WangPMC6321668https://pmc.ncbi.nlm.nih.gov/articles/PMC6321668/0
2018Gambogic acid-induced autophagy in nonsmall cell lung cancer NCI-H441 cells through a reactive oxygen species pathwayLijun Ye30539827https://pubmed.ncbi.nlm.nih.gov/30539827/0
2017Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancerHong PanPMC5652772https://pmc.ncbi.nlm.nih.gov/articles/PMC5652772/0
2016Gambogic Acid Inhibits Malignant Melanoma Cell Proliferation Through Mitochondrial p66shc/ROS-p53/Bax-Mediated ApoptosisLili Liang27119348https://pubmed.ncbi.nlm.nih.gov/27119348/0
2015Gambogic acid induces apoptotic cell death in T98G glioma cellsMya Thida26631318https://pubmed.ncbi.nlm.nih.gov/26631318/0
2015Gambogic acid sensitizes resistant breast cancer cells to doxorubicin through inhibiting P-glycoprotein and suppressing survivin expressionShengpeng Wang25824409https://pubmed.ncbi.nlm.nih.gov/25824409/0
2014Gambogic acid induces apoptosis in hepatocellular carcinoma SMMC-7721 cells by targeting cytosolic thioredoxin reductaseDongzhu Duan24407164https://pubmed.ncbi.nlm.nih.gov/24407164/0
2014Calcium channel blocker verapamil accelerates gambogic acid-induced cytotoxicity via enhancing proteasome inhibition and ROS generationNingning Liu24373880https://pubmed.ncbi.nlm.nih.gov/24373880/0
2013Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signallingL-H WangPMC3899775https://pmc.ncbi.nlm.nih.gov/articles/PMC3899775/0
2013Gambogic acid sensitizes ovarian cancer cells to doxorubicin through ROS-mediated apoptosisJianxia Wang23436279https://pubmed.ncbi.nlm.nih.gov/23436279/0
2013Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cellsJingyan XuPMC3626980https://pmc.ncbi.nlm.nih.gov/articles/PMC3626980/0
2012Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cellsChenglin Li23194187https://pubmed.ncbi.nlm.nih.gov/23194187/0
2012Gambogic acid deactivates cytosolic and mitochondrial thioredoxins by covalent binding to the functional domainJing Yang22663155https://pubmed.ncbi.nlm.nih.gov/22663155/0
2012Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROSLI-JING YANGPMC3389632https://pmc.ncbi.nlm.nih.gov/articles/PMC3389632/0
2011Anti-cancer natural products isolated from chinese medicinal herbsWen TanPMC3149025https://pmc.ncbi.nlm.nih.gov/articles/PMC3149025/?report=classic0
2007Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathwayManoj K PandeyPMC2077305https://pmc.ncbi.nlm.nih.gov/articles/PMC2077305/0