Estragole / Dose Cancer Research Results

ESTr, Estragole: Click to Expand ⟱
Features: Toxic

Estragole is a cautionary/toxicology-relevant natural product because it is a naturally occurring phenylpropene found in several medicinal/aromatic plants and is widely discussed as a genotoxic carcinogenic concern. EFSA describes estragole in fennel seed preparations as a naturally occurring compound that is genotoxic and carcinogenic, and EMA/HMPC recommends keeping exposure to estragole as low as practically achievable in herbal medicinal products.

Estragole — Estragole is a naturally occurring phenylpropene aromatic compound, also known as methyl chavicol or p-allylanisole, found in tarragon, basil, fennel, anise, star anise, chervil, and related essential oils. It is best classified in this database as a toxicology-relevant natural-product constituent rather than an anticancer therapeutic agent. Its main database relevance is genotoxic carcinogenic risk after metabolic activation, especially from concentrated essential oils or high-estragole herbal preparations.

Primary mechanisms (ranked):

  1. CYP-mediated 1′-hydroxylation followed by sulfotransferase bioactivation to reactive 1′-sulfooxyestragole.
  2. Covalent DNA adduct formation and genotoxic initiation, especially in liver-relevant metabolic systems.
  3. Rodent hepatocarcinogenesis after repeated or high-dose exposure, with human relevance inferred from shared metabolic activation pathways.
  4. Direct DNA damage and weak direct-acting genotoxicity in vitro, with apoptosis only at high experimental concentrations.
  5. Competing detoxification pathways such as O-demethylation, oxidation, glucuronidation, and other conjugation routes that reduce relative bioactivation at lower exposures.

Bioavailability / PK relevance: Estragole is a small lipophilic volatile compound with oral and dermal exposure relevance. Oral exposure is rapidly metabolized, and the risk-relevant pathway depends on formation of 1′-hydroxyestragole and subsequent sulfoconjugation. Concentrated oils, extracts, supplements, and repeated medicinal use are more relevant than ordinary low culinary exposure.

In-vitro vs systemic exposure relevance: Many in-vitro genotoxicity or cytotoxicity studies use high micromolar to millimolar concentrations that exceed typical dietary spice exposure. However, estragole is treated as a genotoxic carcinogen in risk assessment because DNA-reactive metabolites can form in human-relevant systems, and a safe exposure threshold has not been firmly established by regulators.

Clinical evidence status: No credible anticancer clinical use. Evidence status is toxicology/regulatory: rodent carcinogenicity, mechanistic genotoxicity, human metabolite evidence, and regulatory exposure-minimization guidance. Database classification should emphasize hazard, exposure control, and caution with high-estragole essential oils or concentrated herbal medicinal products.

Estragole Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 CYP and SULT bioactivation ↔ therapeutic relevance unclear ↑ 1′-hydroxyestragole and ↑ reactive sulfate metabolite R Metabolic activation Core hazard mechanism; liver metabolism is central to genotoxic carcinogenicity.
2 DNA adduct formation ↑ DNA adduct stress (model-dependent) ↑ covalent DNA binding and genotoxic initiation R/G Genotoxic carcinogenic risk Primary database pathway; should be listed as toxic/pro-carcinogenic rather than anticancer.
3 Hepatocarcinogenesis ↔ not a treatment mechanism ↑ liver tumor risk in rodent high-dose/repeated exposure models G Tumor initiation and promotion risk Rodent liver tumor evidence drives regulatory concern; human risk is inferred through shared metabolic activation.
4 DNA damage response and apoptosis ↑ apoptosis only at high concentration ↑ DNA damage stress (dose-dependent) G Nonselective cytotoxic stress In-vitro apoptosis findings are not a practical anticancer rationale because they occur at high exposure and are outweighed by genotoxic risk.
5 NRF2 sensitization assay signal ↔ unclear ↑ ARE-NRF2 reporter signal in skin-sensitization testing R/G Electrophile/stress-response signal NRF2 is not a core anticancer mechanism here; it appears mainly in hazard testing for sensitization or reactive chemistry.
6 Detoxification competition ↔ context-dependent ↑ detoxification via O-demethylation and conjugation pathways R Risk modulation Low-dose risk may be reduced by competing detoxification, but this does not establish a safe threshold.
7 Clinical Translation Constraint Not suitable as anticancer product Genotoxic carcinogen concern; avoid concentrated exposure G Regulatory and safety limitation Database use should emphasize toxicology, exposure minimization, and caution with fennel oil, anise oil, star anise oil, basil oil, and tarragon oil sources.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr
Dose, Dosage: Click to Expand ⟱
Source:
Type:
Drug dosage vs efficacy, and actual dosage number of research papers.
Scientific Papers found: Click to Expand⟱
6425- ESTr,    Assessing the Risk of Estragole Consumption From Natural Products in the Malaysian Market by Using the Margin of Exposure Approach
- Review, Nor, NA
*toxicity↑, *Dose↝,

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:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance ⓘ

Dose↝, 1,  

Functional Outcomes ⓘ

toxicity↑, 1,  
Total Targets: 2

Scientific Paper Hit Count for: Dose, Dosage
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#:403  Target#:1114  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page