Arctigenin / AR 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
AR, androgen receptor: Click to Expand ⟱
Source: HalifaxProj(suppress signaling);CGL-Driver Genes
Type: Oncogene
Androgens play an important role in the proliferation, differentiation, maintenance and function of the prostate [1]. Intriguingly, they may also be involved in the development and progression of prostate cancer. Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen.

The prognostic significance of androgen receptor expression varies widely across different cancer types. In some cancers, high AR expression is associated with poor outcomes, while in others, it may indicate a better prognosis
High expression with poor prognosis is most common.

AR is used as a clinical biomarker for prostate therapy
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: AR, androgen receptor
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#:15  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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