Gallic acid / TumCI Cancer Research Results

GA, Gallic acid: Click to Expand ⟱
Features:
Phenolic acid found in gallnuts, sumac, witch hazel, tea leaves, oak bark. Has antioxidant, antimicrobial and anti-obesity properties.
The GA derivatives include two types: ester and catechin derivatives. The most common ester derivatives of GA are alkyl esters, which are composed mainly of methyl gallate (MG), propyl gallate (PG), octyl gallate (OG), dodecyl gallate (DG), tetradecyl gallate (TG), and hexadecyl gallate (HG), and some of the main catechin derivatives are epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), gallocatechin gallate (GCG), and epigallocatechin gallate (EGCG)

Gallic acid is a naturally occurring polyphenol found in a variety of plant-based foods. Some of the best dietary sources include:

Fruits:
Berries (strawberries, blackberries, blueberries)
Grapes, including red wine (grapes are rich in polyphenols)
Pomegranates and apples
Nuts and Seeds: Walnuts and almonds have been noted to contain GA in their skins
Herbs and Spices: Tea (especially green tea), Sumac and other spices
Other Plants: Gallnuts (from oak trees)

Pathways:
-ROS generation in tumor cells is frequently reported, Antioxidant behavior dominates in normal tissue models -Apoptosis Induction: Activating caspase cascades, Shifting Bax versus Bcl-2, MMP, cyt-c release -Cell Cycle Arrest: typ @ G1 or G2/M checkpoints.
-Anti-inflammatory Effects: inhibiting NF-κB
-reported Angiogenesis Inhibition:
-Modulation of Signaling Pathways: MAPK Pathway, PI3K/Akt Pathway Inhibition, p53 Pathway

Gallic acid exhibits a complex behavior with ROS in cancer cells, acting as both an antioxidant and a pro-oxidant depending on the context and its concentration:

Antioxidant Effects at Low Doses:
-At lower concentrations, gallic acid is typically characterized by its ability to scavenge free radicals, thus reducing oxidative stress.
This antioxidant property may help protect normal cells from DNA damage, reducing the risk of mutations that could lead to cancer.

Pro-oxidant Effects at High Doses: >50-100uM?
-Capable of biphasic redox behavior (antioxidant in normal cells, pro-oxidant in some tumor contexts) -At higher concentrations, GA can exert pro-oxidant effects, generating ROS within cancer cells. Elevated ROS levels can overwhelm the cellular antioxidant defenses of cancer cells, leading to oxidative stress, mitochondrial dysfunction, and ultimately cell death.

Oral bioavailability is well absorbed but subject to rapid conjugation (glucuronide/sulfate/methylated metabolites). Many cytotoxic in-vitro concentrations are in the 10–100 µM range, often higher than typical plasma levels after dietary intake.

Gallic acid — Gallic acid is a naturally occurring trihydroxybenzoic phenolic acid and plant secondary metabolite with antioxidant, pro-oxidant, anti-inflammatory, antimicrobial, and extensively studied preclinical anticancer activity. It is formally classified as a low-molecular-weight polyphenolic phenolic acid and is commonly abbreviated GA. Its chemical identity is 3,4,5-trihydroxybenzoic acid. Dietary and botanical sources include gallnuts, sumac, tea, grapes, berries, pomegranate, mango, walnuts, oak bark, and hydrolysable tannins. GA is also released during digestion or microbial metabolism of gallotannins and galloylated polyphenols. Its anticancer effects are strongly concentration-, cell-type-, redox-, and exposure-dependent.

Primary mechanisms (ranked):

  1. Biphasic redox modulation, with ROS generation and oxidative stress predominating in susceptible cancer cells at cytotoxic concentrations, but ROS scavenging and NRF2-linked antioxidant protection predominating in many normal or inflamed tissues.
  2. Mitochondrial apoptosis through mitochondrial membrane depolarization, Bax/Bcl-2 imbalance, cytochrome-c release, caspase activation, and PARP cleavage.
  3. Suppression of oncogenic survival signaling, particularly PI3K/AKT, STAT3, EGFR, and context-dependent MAPK signaling.
  4. Cell-cycle arrest through modulation of p53, p21, p27, cyclins, and cyclin-dependent kinases, commonly at G1 or G2/M depending on the model.
  5. Suppression of inflammatory and tumor-promoting transcription through NF-κB inhibition and reduced COX-2, IL-6, TNF-α, and related mediators.
  6. Inhibition of angiogenesis through PTEN/AKT/HIF-1α/VEGF signaling and reduced endothelial or tumor-associated vascular responses.
  7. Suppression of invasion, migration, epithelial-mesenchymal transition, and matrix-remodelling pathways, including MMP2, MMP9, Wnt/β-catenin, and selected EMT regulators.
  8. Metabolic disruption through context-dependent inhibition of glycolysis, LDH-associated lactate metabolism, lipid synthesis, and other tumor bioenergetic processes.
  9. Therapy sensitization reported with selected cytotoxic and targeted agents, including paclitaxel, carboplatin, camptothecin, and olaparib, but currently supported mainly by cell-culture evidence.

Bioavailability / PK relevance: GA can be absorbed orally and is among the more readily absorbed simple polyphenols, but absorption is followed by rapid methylation, glucuronidation, sulfation, microbial transformation, and urinary elimination. Circulating exposure consists substantially of conjugated and microbial metabolites rather than persistent free GA. Formulation strategies such as nanoparticles, conjugates, and encapsulation can increase exposure experimentally, but these delivery systems remain investigational.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM GA, with pronounced pro-oxidant cytotoxicity frequently occurring toward the upper portion of this range or above it. These free-compound concentrations commonly exceed sustained plasma concentrations expected from ordinary dietary intake. Consequently, direct systemic anticancer effects demonstrated at high micromolar exposure may not be achievable through food consumption or conventional oral supplementation. Local gastrointestinal exposure, metabolites, tissue accumulation, or engineered delivery could produce different exposure relationships.

Clinical evidence status: Preclinical. GA has extensive cell-culture evidence and a smaller body of animal evidence across multiple tumor types. Human pharmacokinetic and food-intervention studies confirm exposure to GA and its metabolites, but isolated GA has not established anticancer efficacy in randomized clinical trials and is not an approved cancer therapy. Human studies involving polyphenol-rich mango, pomegranate, tea, grape, or botanical preparations cannot be attributed specifically to GA. Therapy-sensitizing activity remains experimental and should not be used to justify combining GA supplements with chemotherapy outside clinical supervision.

Gallic Acid Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Biphasic redox modulation ROS ↑; oxidative stress ↑ (dose-dependent) (model-dependent) ROS ↓; radical scavenging ↑; antioxidant capacity ↑ P, R Selective redox destabilization Pro-oxidant tumor effects are most evident at higher in-vitro concentrations; antioxidant effects dominate in many non-malignant injury models.
2 Mitochondrial apoptosis Mitochondrial membrane potential ↓; Bax ↑; Bcl-2 ↓; cytochrome-c ↑; caspases ↑; PARP cleavage ↑ ↔ or apoptosis ↓ under oxidative injury (context-dependent) R, G Intrinsic apoptotic cell death Frequently downstream of ROS accumulation, although mitochondrial and apoptotic responses vary by tumor genotype and concentration.
3 PI3K AKT survival signaling PI3K ↓; p-AKT ↓; mTOR signaling ↓ (model-dependent); PTEN ↑ ↔ or AKT-associated cytoprotection ↑ during inflammatory injury R, G Growth and survival suppression Direction can differ between malignant cells and stressed normal tissues; pathway effects should be entered with context qualifiers.
4 Cell-cycle checkpoints p53 ↑; p21 ↑; p27 ↑; cyclin D1 ↓; cyclin E ↓; G1 or G2/M arrest ↑ ↔ G Cytostasis Arrest phase is model-dependent and should not be generalized to one checkpoint.
5 NF-κB inflammatory signaling NF-κB ↓; COX-2 ↓; IL-6 ↓; TNF-α ↓; pro-survival inflammation ↓ NF-κB ↓; inflammatory cytokines ↓; epithelial protection ↑ R, G Anti-inflammatory and anti-survival signaling One of the more reproducible effects across tumor and non-tumor inflammatory models.
6 MAPK stress signaling JNK ↑; p38 ↑; ERK ↓ or ↔ (context-dependent) Pathologic p38 and ERK activation ↓ or protective signaling ↑ (context-dependent) P, R Stress-response reprogramming MAPK direction depends on cell type, initiating stress, exposure duration, and whether apoptosis or cytoprotection is being measured.
7 Angiogenesis and hypoxia signaling PTEN ↑; AKT ↓; HIF-1α ↓; VEGF ↓; angiogenesis ↓ ↔ G Anti-angiogenic activity Supported by selected ovarian, cervical, and other experimental cancer models; not clinically validated.
8 Invasion and epithelial-mesenchymal transition MMP2 ↓; MMP9 ↓; Wnt/β-catenin ↓; EMT ↓; migration ↓; invasion ↓ ↔ or epithelial barrier integrity ↑ G Anti-invasive phenotype Often secondary to NF-κB, AKT, MAPK, and Wnt pathway modulation.
9 NRF2 antioxidant response NRF2 ↑ or ↓ (context-dependent); HO-1 ↑ or ↓; redox adaptation altered NRF2 ↑; HO-1 ↑; GSH ↑; SOD ↑; catalase ↑ R, G Secondary redox adaptation NRF2 activation is generally cytoprotective in normal tissue but may protect some cancers; prostate-cancer findings indicate model-dependent alteration of the NRF2 HO-1 BACH1 axis.
10 Glycolysis and lipid metabolism LDH activity ↓; lactate production ↓; FASN ↓; glycolytic dependence ↓ (model-dependent) ↔ R, G Metabolic growth restriction The evidence base is smaller and less consistent than that for redox modulation and apoptosis; avoid treating glycolysis inhibition as universal.
11 DNA damage and repair balance DNA damage ↑; p53 response ↑; FEN1 ↓ in nanoparticle studies; repair capacity ↓ (model-dependent) Oxidative DNA damage ↓ at antioxidant exposure R, G Genotoxic stress in cancer cells Free GA and GA-containing nanocarriers are not mechanistically interchangeable; nanoparticle-specific findings require separate qualification.
12 Chemosensitization Paclitaxel response ↑; carboplatin response ↑; camptothecin response ↑; olaparib response ↑ (model-dependent) Chemotherapy-associated injury ↓ or ↔ in limited models G Adjunctive treatment sensitization Evidence is primarily in vitro. Both antioxidant protection and pro-oxidant sensitization are possible, making unsupervised clinical combinations inappropriate.
13 Immune checkpoint and tumor immunity PD-L1 ↓; CD8-positive T-cell activity ↑; antitumor immune response ↑ (model-dependent) Immune homeostasis modulation ↔ G Immune sensitization Promising animal evidence exists, but direct clinical immunotherapy enhancement has not been demonstrated.
14 Clinical Translation Constraint Free systemic GA exposure ↓; conjugation ↑; metabolism ↑; cytotoxic target exposure often not reached Dietary exposure generally tolerated; high-dose isolated exposure insufficiently characterized R, G Exposure and evidence limitation Rapid metabolism, uncertain tumor delivery, formulation heterogeneity, high in-vitro concentrations, and absence of isolated-GA cancer trials limit translation.

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⟱
7048- GA,    Natural bioactive gallic acid shows potential anticancer effects by inhibiting the proliferation and invasiveness behavior in human embryonic carcinoma cells
- in-vitro, Var, NA
AntiCan↑, TumCCA↑, angioG↓, TumCMig↓, TumMeta↓, CSCs↓, Apoptosis↑, P21↑, P53↑, p27↑, CDK4↓, cycE/CCNE↓, cycD1/CCND1↓, SOX2↓, Nanog↓, OCT4↓, ROS↑, DNAdam↑, BRCA1↑, ATM↑, CHK1↑, Chk2↑, Histones↑, TumCI↓, MMPs↓, EGFR↓, JAK2↓, STAT5↓,
7046- GA,    Gallic acid: A promising anti-non-small cell lung cancer compound targeting early growth response protein-1 for apoptosis and ferroptosis
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H1299
TumCP↓, TumCCA↑, TumCMig↓, TumCI↓, Apoptosis↑, Ferroptosis↑, THBS1↓, EGR1↓, TGF-β1↓, SMAD2↓, SMAD3↓, GPx4↓, ROS↑, i-MDA↑, i-Iron↑,
7041- GA,    Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway
- vitro+vivo, RCC, 786-O - in-vitro, RCC, ACHN - in-vitro, Nor, HK-2
selectivity↑, TumCP↓, TumCMig↓, TumCI↓, TumCCA↑, TumVol↓, TumW↓, Ki-67↓, MMP9↓, TumAuto↑, LC3B-II↓, Beclin-1↓, p62↑,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   i-Iron↑, 1,   i-MDA↑, 1,   ROS↑, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Histones↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 2,   Chk2↑, 1,   Ferroptosis↑, 1,   p27↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1,   LC3B-II↓, 1,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↑, 1,   BRCA1↑, 1,   CHK1↑, 1,   DNAdam↑, 1,   P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 3,  

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

CSCs↓, 1,   Nanog↓, 1,   OCT4↓, 1,   SOX2↓, 1,   STAT5↓, 1,  

Migration(tgid=13) ⓘ

Ki-67↓, 1,   MMP9↓, 1,   MMPs↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   TGF-β1↓, 1,   THBS1↓, 1,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 1,   EGR1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

JAK2↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

BRCA1↑, 1,   EGFR↓, 1,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 51

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
3 Gallic acid
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#:82  Target#:324  State#:%  Dir#:1
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