Grapeseed extract / N-cadherin Cancer Research Results

GSE, Grapeseed extract: Click to Expand ⟱
Features:
Grapeseed extract (GSE) is rich in oligomeric proanthocyanidins (OPCs), catechins, and other polyphenols derived from Vitis vinifera seeds. In cancer research, GSE is most consistently associated with antioxidant and anti-inflammatory signaling modulation, suppression of PI3K/AKT and MAPK pathways, induction of cell-cycle arrest, and promotion of apoptosis in preclinical models. GSE has also been reported to inhibit angiogenesis (via VEGF suppression), reduce metastasis-related markers (e.g., MMPs), and modulate redox balance in tumor cells. Effects are concentration-dependent and vary by tumor type. While GSE is frequently described as antioxidant in normal tissues, pro-oxidant effects have been reported in tumor contexts at higher concentrations. Human oncology data remain limited; most findings derive from in vitro and animal studies.
Made from seeds of grapes and contains antioxidants Vitamin E, linolenic acid and OPCs.

Grapeseed extract — Grapeseed extract (GSE) is a polyphenol-rich botanical extract prepared from seeds of Vitis vinifera, with oligomeric proanthocyanidins/procyanidins as its principal bioactive constituents together with catechin, epicatechin, and related flavan-3-ols. It is classified as a botanical dietary supplement / polyphenolic extract rather than a single molecular drug. Standard abbreviations include GSE, grape seed proanthocyanidin extract (GSPE), and grape seed procyanidin extract. Standardized formulations such as Leucoselect Phytosome complex grape-seed procyanidins with phospholipids to improve oral absorption. Cancer-related effects remain predominantly preclinical, although a small phase I lung-cancer chemoprevention study demonstrated biological activity in human bronchial tissue.

Primary mechanisms (ranked):

  1. Suppression of oncogenic PI3K/AKT signaling, including miR-19a/miR-19b downregulation, PTEN restoration, and reduced AKT phosphorylation in lung-cancer models.
  2. Suppression of proliferative and inflammatory signaling including NF-κB, COX-2, survivin, cyclin D1, and related eicosanoid pathways.
  3. Induction of apoptosis and cell-cycle arrest, including mitochondrial apoptotic signaling and increased CDKN1A/p21 associated with miR-106b suppression.
  4. Suppression of invasion and epithelial-mesenchymal transition through TGF-β/SMAD, MMP, cadherin, and related migration pathways.
  5. Redox modulation: antioxidant activity predominates in normal/nonmalignant tissues, whereas sufficiently high concentrations can produce ROS-dependent mitochondrial stress and apoptosis in some cancer-cell models.
  6. Suppression of angiogenic signaling, including VEGF/VEGFR-related pathways in preclinical models.

Bioavailability / PK relevance: Oral exposure to intact higher-order proanthocyanidin oligomers is limited because polymer size, gastrointestinal stability, metabolism, and microbial degradation restrict systemic absorption. Monomeric flavan-3-ols and smaller metabolites are more readily absorbed. Consequently, biological effects after oral GSE may be mediated substantially by lower-molecular-weight constituents and metabolites rather than by circulating intact oligomeric proanthocyanidins. Phospholipid formulations such as Leucoselect Phytosome were specifically developed to improve exposure.

In-vitro vs systemic exposure relevance: Many direct anticancer experiments expose cancer cells to tens to hundreds of µg/mL of GSE, concentrations that should not be assumed to represent plasma concentrations achievable after conventional oral supplementation. Direct ROS-mediated cytotoxicity and mitochondrial injury are therefore particularly vulnerable to this translation problem. Lower-exposure effects involving inflammatory signaling, circulating metabolites, or tissue microenvironment modulation may be more clinically plausible.

Clinical evidence status: Predominantly preclinical, with small human mechanistic/chemoprevention evidence. A modified phase I study of bioavailability-enhanced Leucoselect Phytosome in eight heavy current/former smokers, six of whom completed treatment, reported good tolerability and approximately 55% reduction in bronchial Ki-67 labeling after three months together with modulation of miR-19a, miR-19b, and miR-106b. Subsequent analysis found reduced pulmonary TNF, CCL3, and granzyme B without significant alteration of CYP3A4 activity. A phase IIa presurgical study in early-stage lung cancer has also been registered, but GSE is not an established or approved cancer treatment and there is no evidence from adequately powered randomized oncology trials demonstrating improved tumor response, progression-free survival, or overall survival.

Grapeseed Extract Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 miR-19 PTEN PI3K AKT axis miR-19a/b ↓; PTEN ↑; p-AKT ↓ ↔ (context-dependent) R, G Growth and survival signaling ↓ One of the better-defined GSE mechanisms in lung-cancer models and supported by biomarker modulation in the small human chemoprevention study.
2 NF-κB COX-2 inflammatory survival signaling NF-κB ↓; COX-2 ↓; PGE2 ↓; survivin ↓ Inflammatory signaling ↓ R, G Inflammation and survival ↓ Observed across colon, skin, and lung-related experimental systems. Human pulmonary studies also show reductions in selected inflammatory mediators.
3 Apoptosis and mitochondrial signaling Apoptosis ↑; Bax/Bcl-2 ratio ↑; caspase activity ↑; mitochondrial dysfunction ↑ (model-dependent) Apoptosis ↔ at lower exposure R, G Tumor-cell death ↑ Frequently observed at cytostatic or cytotoxic GSE concentrations; quantitative clinical relevance is constrained by oral exposure.
4 miR-106b CDKN1A cell-cycle axis miR-106b ↓; CDKN1A/p21 ↑; proliferation ↓ ↔ G Cell-cycle arrest ↑ Mechanistically characterized in lung-neoplastic cells; complements cyclin D1 suppression reported in other tumor models.
5 Cell-cycle proliferation program Cyclin D1 ↓; Ki-67 ↓; proliferation ↓ Minimal suppression at typical noncytotoxic exposure G Cytostasis ↑ Bronchial Ki-67 decreased in the small phase I Leucoselect Phytosome study, providing limited human biomarker support.
6 TGF-β SMAD EMT invasion axis p-SMAD2/3 ↓; N-cadherin ↓; vimentin ↓; E-cadherin ↑; EMT ↓ ↔ G Migration and invasion ↓ Supported particularly in bladder-cancer and other metastatic models.
7 MMP extracellular-matrix remodeling MMP2 ↓; MMP9 ↓; invasion ↓ MMP activity ↓ (context-dependent) G Metastatic potential ↓ Likely partly downstream of NF-κB, TGF-β, and MAPK modulation.
8 VEGF angiogenic signaling VEGF ↓; VEGFR signaling ↓; angiogenesis ↓ Angiogenesis ↓ (context-dependent) G Tumor vascularization ↓ Primarily preclinical evidence; systemic concentrations required for direct antiangiogenic activity remain uncertain.
9 ROS mitochondrial stress ROS ↑; mitochondrial membrane dysfunction ↑; oxidative DNA damage ↑ (high concentration only) ROS ↓; oxidative damage ↓ P, R Selective redox stress Biphasic behavior is important: GSE is generally antioxidant systemically but can become pro-oxidant in cancer cells under sufficiently high experimental exposure.
10 NRF2 antioxidant defense ↔ or ↑ (context-dependent) NRF2 ↑; antioxidant defenses ↑ R, G Oxidative-stress protection Secondary rather than a defining anticancer mechanism. Activation may protect normal tissue but theoretically could also support antioxidant defenses in some tumors.
11 Pulmonary inflammatory microenvironment Migration/invasion ↓ when exposed to post-treatment BAL fluid TNF ↓; CCL3 ↓; granzyme B ↓ G Pro-tumor inflammatory environment ↓ Observed in a very small human Leucoselect Phytosome cohort and therefore biologically interesting but not evidence of therapeutic efficacy.
12 Clinical Translation Constraint Direct cytotoxic exposure difficult to reproduce systemically Generally well tolerated in short human studies — Translation limited Complex extract composition, poor absorption of larger proanthocyanidins, metabolite-dependent exposure, formulation differences, small human studies, and absence of definitive oncology RCT outcomes substantially limit clinical inference.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr
N-cadherin, N-cadherin: Click to Expand ⟱
Source:
Type:
Also known as Cadherin2 (CDH2).
N-cadherin is a type of cell adhesion molecule that plays a crucial role in the development and maintenance of tissue structure. In the context of cancer, N-cadherin has been implicated in the progression and metastasis of various types of tumors.
N-cadherin expression is increased in various types of cancer.
Normally, N-cadherin is expressed in mesenchymal cells, such as fibroblasts and smooth muscle cells. However, in cancer cells, N-cadherin expression is often upregulated, which can contribute to the epithelial-to-mesenchymal transition (EMT). EMT is a process by which epithelial cells acquire a more mesenchymal phenotype, which is characterized by increased motility, invasiveness, and resistance to apoptosis.
The expression of N-cadherin in cancer cells is closely associated with tumorigenesis and metastasis. Additionally, the soluble N-cadherin level in the serum of cancer patients is much higher than that in the serum of healthy patients, revealing a positive relation with poor prognosis.
Scientific Papers found: Click to Expand⟱
1118- GSE,    Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF- β Signaling Pathway
- in-vitro, Bladder, T24/HTB-9 - in-vitro, Bladder, 5637
TumCMig↓, TumCI↓, MMP2↓, MMP9↓, EMT↓, N-cadherin↓, Vim↓, Slug↓, E-cadherin↑, ZO-1↑, p‑SMAD2↓, p‑SMAD3↓, p‑Akt↓, p‑ERK↓, p‑p38↓,
1240- GSE,  PACs,    Grape Seed Proanthocyanidins Inhibit Melanoma Cell Invasiveness by Reduction of PGE2 Synthesis and Reversal of Epithelial-to-Mesenchymal Transition
- in-vitro, Melanoma, A375 - in-vitro, Melanoma, Hs294T
TumCMig↓, TumCI↓, COX2/PTGS2↓, PGE2↓, NF-kB↓, EMT↓, E-cadherin↑, Vim↓, Fibronectin↓, N-cadherin↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death(tgid=5) ⓘ

p‑Akt↓, 1,   p‑p38↓, 1,  

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

EMT↓, 2,   p‑ERK↓, 1,  

Migration(tgid=13) ⓘ

E-cadherin↑, 2,   Fibronectin↓, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 2,   Slug↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   Vim↓, 2,   ZO-1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   NF-kB↓, 1,   PGE2↓, 1,  
Total Targets: 19

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: N-cadherin, N-cadherin
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#:91  Target#:355  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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