Cynara scolymus/Globe Artichoke/Artichoke Extract / COX2/PTGS2 Cancer Research Results

CS, Cynara scolymus/Globe Artichoke/Artichoke Extract: Click to Expand ⟱
Features:

Cynara scolymus - Globe Artichoke / Artichoke Extract,, Artichoke leaf extract

Type: Botanical extract / polyphenol-rich medicinal plant

Active Constituents: Cynarin, chlorogenic acid, caffeoylquinic acids, luteolin, apigenin, and related flavonoids and phenolic compounds.

Function: Cynara scolymus exhibits antioxidant, anti-inflammatory, hepatoprotective, lipid-modulating, metabolic, and cytoprotective effects. Artichoke extracts can modulate oxidative stress, inflammatory signaling, apoptosis, and cellular metabolism.

Cancer: Experimental studies indicate antiproliferative, pro-apoptotic, antioxidant, and anti-inflammatory effects in multiple cancer cell models, with potential modulation of cell-cycle and survival pathways.

Alzheimer's Disease: Preclinical evidence suggests neuroprotective effects through antioxidant, anti-inflammatory, and cholinergic mechanisms, but the evidence base is less developed than for its metabolic and hepatic effects.


For supplements look for: standardized caffeoylquinic acids per capsule (example 5%, 25mg/capsule)

Cynara scolymus — globe artichoke, commonly used medicinally as artichoke leaf extract (ALE), is a polyphenol- and sesquiterpene-lactone-rich botanical preparation derived primarily from the leaves of Cynara cardunculus L. subsp. scolymus, historically also designated Cynara scolymus L. It is classified as a botanical extract / herbal medicinal product rather than a single defined drug. Common abbreviations are CS and ALE. Major constituents include chlorogenic acid and other caffeoylquinic acids, cynarin, luteolin glycosides, apigenin derivatives, and the sesquiterpene lactone cynaropicrin; their concentrations vary substantially with plant part, cultivar, extraction method, and standardization. Artichoke leaf preparations have established traditional gastrointestinal use and human clinical investigation for dyslipidemia and metabolic/liver disorders, whereas anticancer activity remains predominantly preclinical.

Primary mechanisms (ranked):

  1. Induction of mitochondrial apoptosis through ↑BAX, ↓BCL-2, mitochondrial dysfunction, and caspase-9/caspase activation.
  2. Cell-cycle arrest and durable growth suppression, including G2/M arrest and p16/p21-associated cellular senescence.
  3. Context-dependent pro-oxidant ROS accumulation in cancer cells, contributing to apoptosis, senescence, DNA damage, and chemosensitization.
  4. Suppression of proliferative and inflammatory survival signaling, including ↓NF-κB activity in susceptible cancer models.
  5. Suppression of cancer-cell invasion and metastatic phenotype in breast-cancer models.
  6. FEN1 downregulation and increased DNA-damage susceptibility, enhancing sensitivity to DNA-damaging chemotherapy such as paclitaxel in preclinical breast-cancer models.
  7. Antioxidant and cytoprotective activity in non-malignant tissues through polyphenol-mediated reduction of oxidative injury; this contrasts with the pro-oxidant response observed in some cancer models.

Bioavailability / PK relevance: Artichoke extract is a complex mixture rather than a single systemically delivered compound. Human pharmacokinetic studies demonstrate absorption and extensive metabolism of caffeoylquinic acids and flavonoids, with circulating metabolites such as caffeic/dihydrocaffeic-acid derivatives and conjugated flavonoids likely contributing to biological activity. Parent polyphenol exposure is relatively low and extensively transformed by intestinal, hepatic, and microbial metabolism. Extract composition and standardization are therefore major determinants of exposure.

In-vitro vs systemic exposure relevance: Many anticancer experiments use whole artichoke extracts at concentrations in the tens to hundreds of µg/mL range or prolonged cellular exposure. These conditions cannot be assumed to reproduce concentrations of intact extract constituents in human tumors after oral supplementation. Human circulating concentrations of individual absorbed polyphenols are generally in the submicromolar-to-low-micromolar range and are dominated by metabolites; consequently, direct extrapolation of cytotoxic in-vitro concentrations to oral systemic anticancer activity is not justified.

Clinical evidence status: Cancer: preclinical only; no established anticancer efficacy in humans and no validated role as cancer therapy or adjunct treatment. Non-cancer indications: multiple small randomized human trials and meta-analyses report effects on lipid parameters, and clinical studies have evaluated metabolic and hepatic outcomes. European herbal-medicine recognition is based principally on traditional use for dyspeptic gastrointestinal complaints rather than cancer treatment.

Safety / translation constraints: Artichoke leaf preparations are generally well tolerated in short-term human studies, but gastrointestinal adverse effects and allergic reactions can occur. Avoid in patients with hypersensitivity to artichoke or other Asteraceae plants. Because artichoke can stimulate bile secretion, bile-duct obstruction and cholangitis are important contraindications, and gallstones or other biliary disorders warrant medical assessment. Extract-to-extract chemical heterogeneity and the large exposure gap between many cell-culture experiments and oral human dosing are major constraints on anticancer translation.

Cancer-Relevant Mechanisms of Cynara scolymus Extract

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial apoptosis ↑ BAX, ↑ caspase-9, ↓ BCL-2, ↑ apoptosis ↔ / cytoprotective (context-dependent) R-G Programmed cancer-cell death Supported in oral squamous carcinoma and colorectal cancer models. Colon-cancer studies indicate activation of the mitochondrial-dependent apoptotic pathway.
2 Cell-cycle arrest and senescence ↑ G2/M arrest, ↑ p16, ↑ p21, ↑ senescence ↔ (model-dependent) G Suppression of proliferation G2/M arrest has been demonstrated in oral squamous carcinoma cells; prolonged low-dose exposure in MDA-MB-231 breast-cancer cells produces p16/p21-associated premature senescence.
3 ROS-mediated cancer stress ↑ ROS (dose-dependent), ↑ oxidative signaling ↓ oxidative stress P-G Apoptosis and senescence Artichoke polyphenols can behave as pro-oxidants in cancer cells while acting predominantly as antioxidants in non-malignant systems. NAC attenuation of growth inhibition supports a causal ROS component in breast-cancer models.
4 NF-κB and inflammatory survival signaling ↓ NF-κB, ↓ survival signaling ↓ excessive inflammatory signaling R-G Reduced proliferation and inflammation Artichoke leaf extract suppresses NF-κB activity in human leukemic-cell models, in part in association with AKR1B1 inhibition.
5 Invasion and metastatic phenotype ↓ invasion, ↓ metastatic phenotype ↔ G Reduced invasive behavior Polyphenolic artichoke extract reduces invasive potential in MDA-MB-231 breast-cancer cells. The precise molecular determinants appear extract- and model-dependent.
6 FEN1 and DNA damage response ↓ FEN1, ↑ DNA damage susceptibility Uncertain R-G Chemosensitization Artichoke polyphenols enhance chemotherapy response in breast-cancer cells through ROS-associated FEN1 downregulation and altered DNA-damage response.
7 Chemosensitization ↑ sensitivity to paclitaxel and DNA damage (model-dependent) Uncertain G Enhanced chemotherapy effect Observed preclinically with artichoke polyphenols plus paclitaxel; ROS/NRF2 and ERK signaling participate in the combination response. This has not been clinically validated.
8 NRF2 redox response ↕ NRF2 (context-dependent) ↑ antioxidant defense (context-dependent) P-R Redox adaptation NRF2 is involved in the ROS-dependent chemotherapy interaction described in breast-cancer cells but is not sufficiently consistent to classify as a universal primary anticancer mechanism of artichoke extract.
9 Antioxidant cytoprotection ↕ oxidative stress (context-dependent) ↓ ROS, ↓ oxidative injury, ↑ antioxidant capacity R-G Protection of non-malignant tissues Human and experimental non-cancer studies generally support antioxidant activity. This bidirectional redox behavior is important when interpreting apparently contradictory cancer and normal-tissue findings.
10 Clinical Translation Constraint In-vitro anticancer exposure often high Oral preparations generally well tolerated G Limits clinical inference Whole-extract concentrations used for cytotoxicity are not directly comparable with plasma exposure after oral ALE. Polyphenols undergo substantial metabolism, formulations vary chemically, and no clinical anticancer efficacy has been established.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr
COX2/PTGS2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Cyclooxygenase-2 (COX-2) is an enzyme that plays a critical role in the conversion of arachidonic acid to prostaglandins, which are lipid compounds involved in various physiological processes, including inflammation, pain, and fever. COX-2 is an inducible enzyme, meaning its expression is typically low in normal tissues but can be upregulated in response to inflammatory stimuli, growth factors, and certain oncogenic signals.
-Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis.
-COX-2 is an inducible enzyme that is upregulated in response to pro-inflammatory signals, including cytokines (e.g., IL-1β, TNF-α) and growth factors.

COX-2 is often overexpressed in various tumors, including colorectal, breast, lung, and prostate cancers.
The prostaglandins produced by COX-2, particularly prostaglandin E2 (PGE2), have several effects that can facilitate cancer progression:
Cell Proliferation: PGE2 can promote the proliferation of cancer cells by activating signaling pathways such as the PI3K/Akt and MAPK pathways.
Nonselective NSAIDs, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. Epidemiological studies have suggested that regular use of NSAIDs may reduce the risk of certain cancers, particularly colorectal cancer.
Drugs specifically targeting COX-2, such as celecoxib, have been developed.

COX-2 and xanthine oxidase are ROS-producing pro-oxidant enzymes that contribute to inflammation. Elevated COX‑2 levels, often found in inflammatory conditions or certain types of cancers, can contribute to increased production of ROS.
Scientific Papers found: Click to Expand⟱
7415- CS,    Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells
- in-vitro, AML, THP1
AKR1B10↓, NF-kB↓, COX2/PTGS2↓, MMP2↓, ROS↓,

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:


NA, unassigned(tgid=0) ⓘ

AKR1B10↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↓, 1,  

Migration(tgid=13) ⓘ

MMP2↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   NF-kB↓, 1,  
Total Targets: 5

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: COX2/PTGS2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein
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#:443  Target#:66  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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