Arctigenin / NKX3.1 Cancer Research Results

ATG, Arctigenin: Click to Expand ⟱
Features:

Arctigenin — Arctigenin (ATG) is a dibenzylbutyrolactone lignan (the aglycone of arctiin) found notably in Arctium lappa (greater burdock) and related Asteraceae plants. It is a small-molecule natural product investigated for pleiotropic anti-inflammatory and anticancer activities in vitro and in vivo, with reported pathway effects spanning energy-stress signaling, PI3K/AKT–mTOR, and pro-survival transcriptional programs (e.g., STAT3, NF-κB). Common abbreviation: ATG.

Primary mechanisms (ranked):

  1. Energy stress / immunometabolic suppression via AMPK-linked programs, with context-dependent inhibition of glycolysis/ATP generation and preferential cytotoxicity under nutrient stress
  2. PI3K/AKT–mTOR axis suppression, including mTOR pathway inhibition with autophagy-associated cell death in some tumor models
  3. STAT3 pathway inhibition (anti-proliferative / pro-apoptotic signaling shift in multiple cancer models)
  4. NF-κB inflammatory signaling suppression (often downstream of PI3K/AKT/IKK inputs), reducing cytokine/pro-survival transcription in inflammatory disease and some tumor contexts
  5. Cell-death reprogramming (apoptosis/autophagy balance; Bax/Bcl-2-family shifts reported in multiple models)

Bioavailability / PK relevance: Oral exposure is constrained by metabolism: arctiin can be hydrolyzed by gut microbiota to arctigenin; arctigenin is then rapidly conjugated (notably glucuronidation; also sulfation), which can limit free-parent systemic exposure. Human PK exists for a burdock-fruit extract rich in arctigenin (GBS-01), showing measurable exposure with rapid conjugation.

In-vitro vs systemic exposure relevance: Many mechanistic studies use micromolar concentrations; translation depends on whether free (unconjugated) arctigenin reaches comparable levels in target tissues. Conjugation-dominant PK implies that in-vitro potency may overestimate systemic free-drug activity unless delivery/exposure is enhanced or local (GI) effects dominate.

Clinical evidence status: Early human evidence exists (small Phase I oncology study of GBS-01 in advanced pancreatic cancer; supportive PK/safety) plus limited human uptake/safety studies; anticancer efficacy remains unproven in RCTs.

Arctigenin — cancer-relevant mechanistic axes (ranked)

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Energy stress signaling and metabolic vulnerability ↑ metabolic stress; ↓ ATP generation (context-dependent); ↑ death under glucose deprivation Often better tolerance vs tumor metabolic stress (model-dependent) P/R Preferential cytotoxicity in nutrient-stressed tumor states Classic finding: preferential tumor cell death under glucose deprivation via inhibition of energy metabolism (nutrient-stress selectivity).
2 AMPK axis ↑ AMPK activation (context-dependent) → ↓ anabolic drive; can couple to autophagy/translation suppression ↑ AMPK can be cytoprotective under ER/metabolic stress (context-dependent) P/R Energy-sensing shift that can suppress growth programs Multiple primary sources report AMPK activation in stress contexts; note Nestronics lists “AMPKα↓” for pid 33, which may reflect a model-specific readout or a directionality error.
3 PI3K / AKT / mTOR ↓ PI3K/AKT; ↓ mTOR signaling; ↑ autophagy-associated death (model-dependent) ↓ inflammatory PI3K/AKT/IKK signaling in immune/inflammatory settings R/G Growth-pathway suppression; autophagy-linked cytotoxicity in some models Reported in ER+ breast cancer (mTOR inhibition with autophagic cell death) and inflammatory disease models (PI3K/AKT/IKKβ/NF-κB suppression).
4 STAT3 ↓ STAT3 signaling → ↓ proliferation/survival; ↑ apoptosis (model-dependent) Potential ↓ pro-inflammatory STAT3 outputs (context-dependent) R/G Anti-proliferative transcriptional reprogramming Direct STAT3 inhibitory activity is repeatedly reported in cancer models (e.g., TNBC).
5 NF-κB inflammatory axis ↓ NF-κB-dependent survival/invasion programs (context-dependent) ↓ NF-κB activation → ↓ IL-1β/TNF-α/IL-6; ↑ IL-10 signatures (model-dependent) R/G Anti-inflammatory signaling; can indirectly reduce tumor-promoting inflammation Strong preclinical anti-inflammatory evidence; cancer relevance often mediated through TME/inflammation coupling.
6 Cell death balance ↑ apoptosis and/or autophagy-associated death; Bax/Bcl-2-family shifts (model-dependent) Usually less pro-death in normal cells at comparable stress (model-dependent) G Execution of cytotoxic phenotype Frequently downstream of metabolic stress + PI3K/AKT/mTOR + STAT3 changes; direction and dominance vary by model/dose.
7 Clinical Translation Constraint Exposure-limited and conjugation-dominant PK; free-parent levels may be lower than typical in-vitro dosing Same PK constraints; safety margins define usable exposure — PK + formulation and trial-design constraints dominate translation Arctiin→arctigenin gut conversion plus rapid glucuronidation/sulfation are key constraints; Phase I (GBS-01) provides human PK/safety signal but efficacy remains unproven.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
NKX3.1, Homeobox protein Nkx-3.1: Click to Expand ⟱
Source:
Type:
NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Commonly down-regulated in human prostate cancer.
NKX3.1 is a homeobox transcription factor that is normally highly expressed in prostate luminal epithelial cells.

– During prostate tumorigenesis, NKX3.1 expression is frequently downregulated or lost, particularly in higher-grade lesions and advanced disease.
Reduced or absent NKX3.1 expression is generally associated with poor prognosis.
Loss of NKX3.1 leads to:
-Increased oxidative DNA damage
-Impaired DNA repair fidelity
-Dedifferentiation of prostate epithelium
-Increased susceptibility to oncogenic transformation (e.g., cooperation with PTEN loss)

NKX3.1 loss does not drive proliferation directly—it removes safeguards that normally restrain malignant evolution.


Scientific Papers found: Click to Expand⟱
82- QC,  ATG,    Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓, PI3K/Akt↓, miR-21↓, STAT3↓, BAD↓, PRAS40↓, GSK‐3β↓, PSA↓, NKX3.1↑, Bax:Bcl2↑, miR-19b↓, miR-148a↓, AMPKα↓, TumCP↓, chemoPv↑, TumCMig↓,

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 ⓘ

PI3K/Akt↓, 1,  

Cell Death ⓘ

BAD↓, 1,   Bax:Bcl2↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↓, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,  

DNA Damage & Repair ⓘ

NKX3.1↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   STAT3↓, 1,  

Migration ⓘ

miR-148a↓, 1,   miR-19b↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   PRAS40↓, 1,  
Total Targets: 18

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: NKX3.1, Homeobox protein Nkx-3.1
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#:33  Target#:387  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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