Garcinol / TumCI Cancer Research Results

GAR, Garcinol: Click to Expand ⟱
Features:
Found in dried fruit rind of Garcinia Indica with anti-inflammatory, antioxidant, anticancer, and antibacterial properties
Garcinia Cambogia Extract.
"We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol."

🔬1) NF-κB & AP-1 Suppression
Garcinol inhibits NF-κB and AP-1 transcriptional activity in multiple cancer cell systems, reducing pro-inflammatory and pro-survival gene expression.
📚 2) Epigenetic Regulation
Garcinol is one of the few natural products shown to inhibit p300/CBP histone acetyltransferases, shifting chromatin acetylation and influencing gene expression (differentiation, apoptosis, EMT). This is more specific than general “HDAC modulation.”
💀 3) Apoptosis
Studies report modulation of the Bcl-2 family and increased caspase activity, but this is often downstream of transcription/epigenetic changes, not a direct redox trigger.
🧬 4) Cell Cycle & Proliferation
Lower Cyclin D1, higher p21/p27, and G1/S arrest are common phenotypes.
🧭 5) Invasion & Angiogenesis
Garcinol reduces MMP-2/9 and angiogenic markers in multiple tumor cell assays.

Garcinol — a naturally occurring polyisoprenylated benzophenone and polycyclic polyprenylated acylphloroglucinol isolated principally from the dried fruit rind of Garcinia indica, commonly called kokum. It is an experimental phytochemical and pleiotropic epigenetic/signalling modulator, abbreviated GAR and also known as camboginol. Garcinol is best characterized as an inhibitor of lysine and histone acetyltransferases, particularly p300/CBP and PCAF/KAT2B, while also modulating NF-κB, STAT3, PI3K/AKT, inflammatory lipid mediators, apoptosis, and epithelial–mesenchymal plasticity. It is not an approved anticancer drug and should not be equated with whole Garcinia cambogia or hydroxycitric-acid supplements.

Primary mechanisms (ranked):

  1. Inhibition of p300/CBP and PCAF histone acetyltransferase activity, producing broad changes in histone and non-histone protein acetylation, chromatin transcription, DNA-damage responses, and oncogenic gene expression.
  2. Suppression of NF-κB and JAK/Src/STAT3 survival and inflammatory transcription, with reductions in Bcl-2-family proteins, survivin, cyclin D1, VEGF, cytokines, and invasion-associated genes.
  3. Induction of intrinsic and extrinsic apoptosis through mitochondrial membrane-potential loss, cytochrome-c release, Bax/Bcl-2 displacement, caspase activation, DR5 upregulation, and c-FLIP/XIAP suppression.
  4. Suppression of PI3K/AKT/mTOR, FAK/Src/ERK, Wnt/β-catenin, Notch, and cancer-stem-cell signalling in model-dependent settings.
  5. Reversal of epithelial–mesenchymal transition and inhibition of invasion, migration, angiogenesis, and stem-like phenotypes through modulation of E-cadherin, vimentin, ZEB factors, Twist1, MMP-2/9, miR-200-family members, let-7, and related pathways.
  6. Inhibition of inflammatory lipid-mediator enzymes, including 5-lipoxygenase and microsomal prostaglandin E synthase-1, reducing leukotriene and PGE2-associated signalling.
  7. ROS elevation and oxidative-stress-mediated apoptosis in selected cancer models; this is secondary and context-dependent because garcinol can also act as a direct antioxidant or radical scavenger in cell-free and non-cancer systems.
  8. Chemosensitization and radiosensitization through suppression of survival and EMT pathways and, for radiation, inhibition of p300/CBP-dependent non-homologous end joining.

Bioavailability / PK relevance: Garcinol is highly lipophilic and poorly water-soluble, making oral absorption and formulation important translational variables. Rat studies reported approximately 27–36% absolute oral bioavailability at oral doses of 22.5–45 mg/kg, with dose-dependent exposure and substantial tissue distribution. Human liver-microsome data suggest intermediate metabolic clearance, but no validated human cancer PK, therapeutic plasma range, or clinically established dose is available. Nanoparticles, phospholipid complexes, cyclodextrins, and other delivery systems may improve exposure, but remain preclinical.

In-vitro vs systemic exposure relevance: Most anticancer experiments use approximately 5–50 µM garcinol, frequently around 10–25 µM. Whether these free concentrations are safely achievable in human tumors is unknown. Rat PK indicates systemic absorption, but it does not establish sustained human exposure comparable with common cell-culture concentrations. Results obtained at 25–100 µM should therefore be treated as high-concentration or mechanistic findings rather than directly clinically achievable effects.

Clinical evidence status: Preclinical. Evidence consists primarily of biochemical assays, cancer-cell studies, organoid or stem-like-cell models, and rodent xenograft or genetically engineered tumor models. Combination activity has been reported with cisplatin, paclitaxel, gemcitabine, TRAIL, curcumin, and ionizing radiation, but no convincing randomized human oncology trial or established adjunctive anticancer use was identified. Garcinol is not approved by FDA, Health Canada, or EMA as a cancer therapy.

Safety / deployment status: A standardized 40% garcinol preparation showed low acute and repeated-dose toxicity in rodent studies, including a reported 90-day no-observed-adverse-effect level of 100 mg/kg/day. These data do not establish long-term human safety, reproductive safety, drug-interaction risk, or safety during chemotherapy. Garcinol can inhibit platelet activation experimentally and modulates acetyltransferases and multiple drug-relevant signalling pathways, creating plausible interaction concerns. Hepatotoxicity reports involving multi-ingredient Garcinia cambogia supplements cannot be attributed specifically to purified garcinol.

Garcinol Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 HAT and HDAC11 epigenetic regulation p300/CBP HAT ↓; PCAF HAT ↓; HDAC11 ↓; histone and non-histone acetylation altered Acetylation-dependent transcription and differentiation may also be altered P, R, G Epigenetic and transcriptional reprogramming HAT inhibition is the dominant and most established direct mechanism. HDAC11 inhibition is supported by biochemical and cellular evidence but is less broadly characterized. Because HAT and HDAC inhibition can have opposing effects on specific lysine residues, net acetylation changes are substrate-dependent rather than uniformly increased or decreased.
2 NF-κB inflammatory survival signalling NF-κB activation ↓; nuclear p65 signalling ↓; COX-2 ↓; IL-6 ↓; anti-apoptotic genes ↓ Inflammatory activation ↓ (context-dependent) R, G Survival and inflammatory transcription suppression Consistent across several cancer models, although the precise acetylation state of p65 can vary by experimental context.
3 JAK Src STAT3 axis JAK1/2 ↓; Src ↓; STAT3 phosphorylation ↓; STAT3 acetylation and dimerization ↓ Not adequately characterized R, G Oncogenic transcription and survival suppression Reduces cyclin D1, Bcl-2, Bcl-xL, Mcl-1, survivin, and VEGF in responsive models.
4 Mitochondrial apoptosis Bax and Bak ↑; Bcl-2 and Bcl-xL ↓; mitochondrial membrane potential ↓; cytochrome c ↑; caspase-9/3 ↑ Generally weaker effects in tested non-tumorigenic cells (model-dependent) R, G Intrinsic apoptotic cell death Usually downstream of survival-pathway, epigenetic, ER-stress, or oxidative-stress modulation.
5 Death receptor and TRAIL signalling DR5 ↑; c-FLIP ↓; XIAP ↓; survivin ↓; caspase-8 ↑; TRAIL sensitivity ↑ Limited sensitization in tested normal-cell models R, G Extrinsic apoptosis and TRAIL sensitization Combination mechanism; clinical efficacy and selectivity have not been established.
6 PI3K AKT mTOR signalling PI3K phosphorylation ↓; AKT phosphorylation ↓; mTOR phosphorylation ↓ Not adequately characterized R, G Growth and survival inhibition Prominent in gastric, ovarian, colorectal, and other selected models but not necessarily a direct universal target.
7 Cell-cycle checkpoints Cyclin D1 ↓; CDK2/4 ↓; p21 ↑; p27 ↑; G1 or G2 arrest ↑ (model-dependent) Possible cytostatic effects at sufficient exposure G Proliferation arrest Checkpoint outcome varies with tumor genotype, p53 status, dose, and exposure duration.
8 EMT invasion and metastasis E-cadherin ↑; vimentin ↓; Twist1 ↓; ZEB1/2 ↓; MMP-2/9 ↓; migration and invasion ↓ Limited data G Anti-invasive and anti-metastatic phenotype Linked to NF-κB, STAT3, p300, TGF-β, Wnt, and miRNA modulation.
9 Cancer stem-cell signalling ALDH1A1 ↓; OCT4 ↓; SOX2 ↓; Notch1 ↓; Wnt/β-catenin ↓; miR-200c and let-7 ↑ Normal stem-cell effects insufficiently characterized G Stem-like phenotype suppression Supported by cell and xenograft models; potential normal progenitor-cell effects require clarification.
10 Inflammatory lipid mediators 5-lipoxygenase ↓; microsomal prostaglandin E synthase-1 ↓; PGE2 ↓ Inflammatory lipid production ↓ P, R Anti-inflammatory and anti-tumor-promoting activity Direct enzyme inhibition is reported at submicromolar to low-micromolar concentrations and may be relevant independently of HAT inhibition.
11 Mitochondrial ROS and ER stress ROS ↑; GSH ↓; CHOP ↑; mitochondrial stress ↑ (context-dependent) ROS scavenging or antioxidant activity may occur (context-dependent) P, R, G Secondary oxidative-stress-mediated apoptosis Bidirectional redox behaviour is likely determined by concentration, cellular redox state, assay system, and tissue context.
12 Angiogenesis and hypoxic signalling VEGF ↓; HIF-1α ↓; CD31 ↓; angiogenesis ↓ Normal vascular effects insufficiently characterized G Reduced tumor vascular support Often downstream of NF-κB, STAT3, PI3K/AKT, PGE2, and invasion-pathway suppression.
13 Chemosensitization Response to cisplatin, paclitaxel, gemcitabine, and TRAIL ↑ (model-dependent) Combination toxicity inadequately defined G Enhanced treatment response Evidence is preclinical; interaction direction may depend on cancer type, schedule, and chemotherapy mechanism.
14 Radiosensitization and DNA repair p300/CBP-dependent non-homologous end joining ↓; radiation response ↑ Normal-tissue radiosensitization insufficiently characterized R, G Impaired DNA double-strand-break repair Potentially therapeutically relevant but currently supported mainly by cell-based evidence.
15 Clinical Translation Constraint Active concentrations commonly 5–50 µM; tumor exposure unknown Human therapeutic window and interaction profile unknown G Limits clinical interpretation Moderate rat oral bioavailability does not establish achievable human tumor concentrations; formulation, purity, metabolism, and long-term safety remain unresolved.

P: 0–30 min    R: 30 min–3 hr    G: >3 hr
TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
830- GAR,    Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src, ERK, and Akt survival signaling in human colon cancer cells
- in-vitro, CRC, HT-29
TumCI↓, TumCMig↓, Apoptosis↑, p‑FAK↓, Src↓, MAPK↓, ERK↓, PI3K/Akt↓, Bax:Bcl2↑, Cyt‑c↑, MMP7↓,
7089- GAR,    Anticancer action of garcinol in vitro and in vivo is in part mediated through inhibition of STAT-3 signaling
- vitro+vivo, BC, MDA-MB-231 - in-vitro, Pca, DU145 - in-vitro, PC, NA
STAT3↓, TumCI↓, NF-kB↓, uPA↓, VEGF↓, MMP9↓,
7091- GAR,    Garcinol-A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug
- Review, Var, NA
antiOx↑, Inflam↓, HATs↓, p300↓, CBP↓, PCAF↓, cycD1/CCND1↓, STAT↓, PI3K↓, Akt↓, TumCP↓, TumCI↓, TumMeta↓, TumCCA↑, CDK2↓, CDK4↓,
802- GAR,    Garcinol acts as an antineoplastic agent in human gastric cancer by inhibiting the PI3K/AKT signaling pathway
- in-vitro, GC, HGC27
TumCP↓, TumCI↓, Apoptosis↑, PI3K/Akt↓, Akt↓, p‑mTOR↓, cycD1/CCND1↓, MMP2↓, MMP9↓, BAX↑, Bcl-2↓,
806- GAR,    Garcinol exerts anti-cancer effect in human cervical cancer cells through upregulation of T-cadherin
- vitro+vivo, Pca, HeLa - vitro+vivo, Cerv, SiHa
TumCI↓, TumCMig↓, TumCCA↑, Apoptosis↑, T-cadherin↑,
812- GAR,    Anti-proliferative and anti-invasive effects of garcinol from Garcinia indica on gallbladder carcinoma cells
- in-vitro, Gall, GBC-SD - in-vitro, Gall, NOZ
TumCG↓, TumCI↓, MMP2↓, MMP9↓,
814- GAR,  PacT,    Garcinol sensitizes breast cancer cells to Taxol through the suppression of caspase-3/iPLA2 and NF-κB/Twist1 signaling pathways in a mouse 4T1 breast tumor model
- in-vivo, BC, NA
Apoptosis↑, TumCCA↑, EMT↓, TumCI↓,
817- GAR,    Garcinol inhibits esophageal cancer metastasis by suppressing the p300 and TGF-β1 signaling pathways
- vitro+vivo, SCC, KYSE150 - vitro+vivo, SCC, KYSE450
HATs↓, TumCCA↑, Apoptosis↑, TumCMig↓, TumCI↓, CBP↓, p300↓, TGF-β↓, Ki-67↓, SMAD2↓, SMAD3↓,

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(tgid=1) ⓘ

antiOx↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

PI3K/Akt↓, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↑, 5,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   CBP↓, 2,   Cyt‑c↑, 1,   MAPK↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

HATs↓, 2,   PCAF↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 2,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   ERK↓, 1,   p‑mTOR↓, 1,   p300↓, 2,   PI3K↓, 1,   Src↓, 1,   STAT↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

p‑FAK↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 3,   SMAD2↓, 1,   SMAD3↓, 1,   T-cadherin↑, 1,   TGF-β↓, 1,   TumCI↓, 8,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 1,   uPA↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

Ki-67↓, 1,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
8 Garcinol
1 Paclitaxel/Taxol
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#:83  Target#:324  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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