Proanthocyanidins / Vim Cancer Research Results

PACs, Proanthocyanidins: Click to Expand ⟱

Features:

Proanthocyanidins (PACs; condensed tannins) = oligomeric/polymeric flavan-3-ols (e.g., catechin/epicatechin units); abundant in grape seed, cocoa, cranberry, apple skin, pine bark. Degree of polymerization (DP) influences bioactivity and absorption.
Primary mechanisms (conceptual rank):
1) Redox modulation → direct ROS scavenging + metal chelation (Fe²⁺/Cu²⁺).
2) NRF2 activation → endogenous antioxidant enzymes (HO-1, NQO1, GCLC).
3) Anti-inflammatory signaling → ↓ NF-κB / ↓ COX-2 / ↓ cytokines.
4) Anti-proliferative / pro-apoptotic signaling in cancer (MAPK, PI3K/Akt modulation; dose-dependent).
5) Anti-angiogenic / anti-metastatic effects (VEGF, MMPs; model-dependent).
PK / bioavailability: monomers/low-DP oligomers absorbed; higher-DP polymers poorly absorbed but metabolized by gut microbiota to phenolic acids; plasma parent PAC levels modest vs many in-vitro studies.
In-vitro vs systemic exposure: many cancer studies use ≥10–100 µM equivalents; achievable circulating levels typically lower and largely conjugated/metabolite-driven.
Clinical evidence status: strongest human data in vascular/cardiometabolic endpoints; oncology evidence largely preclinical/adjunct.

Polyphenols found in cranberry, blueberry, and grape seeds.

Proanthocyanidin B2 (PB2) is a type of dimer flavonoid that is found in grape seed, pine bark, wine, and tea leaves [17]. PB2 has been shown to possess various bioactivities, including anti-oxidant, anti-inflammation, and anti-obesity activities, and it has also shown efficacy in the treatment of cancer, cardiovascular disease, type 2 diabetes, ulcerative colitis, as well as acute liver injury. PKM2 is the target of proanthocyanidin B2

PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.

Proanthocyanidins (PACs) — Cancer-Relevant Pathways

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	ROS tone / redox balance	↓ (low–mod dose); ↑ (high concentration only)	↓	P→R	Antioxidant; metal chelation	Catechol-rich structure scavenges radicals; pro-oxidant shift reported at high doses in tumors (model-dependent).
2	NRF2 axis	↑ (context-dependent)	↑	R→G	Endogenous antioxidant induction	↑ HO-1/NQO1; protective in normal tissue; may support tumor stress resistance (context-dependent).
3	NF-κB / inflammatory signaling	↓	↓	R→G	Anti-inflammatory	Reduces cytokines, COX-2; anti-tumor microenvironment effect plausible.
4	PI3K/Akt / MAPK pathways	↓ proliferation (model-dependent)	↔	R→G	Growth signaling attenuation	Observed in breast, colon, prostate models; dose and DP dependent.
5	Apoptosis (caspase activation)	↑ (dose-dependent)	↔ / ↓	R→G	Pro-apoptotic signaling	Mitochondrial depolarization reported; often supra-physiologic exposure.
6	Angiogenesis (VEGF)	↓ (preclinical)	↔	G	Anti-angiogenic	↓ VEGF expression in models; human oncologic data limited.
7	Ferroptosis axis	↓ (anti-lipid-ROS bias)	↓	P→R	Lipid peroxidation inhibition	Strong antioxidant property may counter ferroptotic strategies (context-dependent).
8	Clinical Translation Constraint	—	—	—	Bioavailability & dose gap	High-DP PACs poorly absorbed; many in-vitro doses exceed realistic plasma exposure; adjunct role most plausible.

TSF Legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr

Proanthocyanidins (PACs) — Alzheimer’s Disease–Relevant Axes

Rank	Pathway / Axis	Cells (neurons/glia)	TSF	Primary Effect	Notes / Interpretation
1	Lipid peroxidation / neuronal ROS	↓	P	Neuroprotective antioxidant	Reduces oxidative damage markers in models; aligns with AD oxidative stress hypothesis.
2	NRF2 activation	↑	R→G	Endogenous antioxidant upregulation	Supports neuronal resilience; mostly preclinical evidence.
3	Neuroinflammation (NF-κB)	↓	R→G	Microglial modulation	Reduced cytokine production in animal models.
4	Aβ aggregation / toxicity	↓ (preclinical)	G	Interference with amyloid aggregation	Reported inhibition of Aβ fibrillization in vitro; human data limited.
5	BDNF / synaptic plasticity	↑ (model-dependent)	G	Neurotrophic signaling	Observed in flavanol-rich cocoa/grape extract studies; translation to PAC isolates unclear.
6	Clinical Translation Constraint	—	—	Dietary-level evidence	Human trials mostly use flavanol-rich extracts; cognitive effects modest and stage-dependent.

TSF Legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr

Vim, Vimentin: Click to Expand ⟱

Source:

Type:

Vimentin, a major constituent of the intermediate filament family of proteins, is ubiquitously expressed in normal mesenchymal cells and is known to maintain cellular integrity and provide resistance against stress. Vimentin is overexpressed in various epithelial cancers, including prostate cancer, gastrointestinal tumors, tumors of the central nervous system, breast cancer, malignant melanoma, and lung cancer. Vimentin’s overexpression in cancer correlates well with accelerated tumor growth, invasion, and poor prognosis; however, the role of vimentin in cancer progression remains obscure.

In many epithelial-derived tumors (carcinomas), elevated Vimentin expression is often observed in cancer cells that have undergone EMT. This upregulation is characteristic of a shift toward a mesenchymal state, which is associated with reduced cell–cell adhesion and increased motility. Vimentin expression is also noted in the tumor stroma, reflecting the presence and activation of mesenchymal cells such as cancer-associated fibroblasts (CAFs). This dual expression can contribute to the remodeling of the tumor microenvironment.
The degree of Vimentin expression may vary depending on the tumor type, grade, and stage. More aggressive and advanced tumors tend to show higher levels of Vimentin expression.

High Vimentin expression has been correlated with poor clinical outcomes in several cancers, including breast, colorectal, prostate, and lung cancers.
Elevated Vimentin levels are typically associated with higher tumor grade, increased invasiveness, enhanced metastatic potential, and a greater risk of recurrence.
As a component of the EMT signature, high Vimentin expression can serve as an indicator of a more aggressive tumor phenotype and is often associated with reduced overall survival.
- vimentin up-regulation is often used as a marker of EMT in cancer

Scientific Papers found: Click to Expand⟱

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↓, PGE2↓, NF-kB↓, EMT↓, E-cadherin↑, Vim↓, Fibronectin↓, N-cadherin↓,

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:

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,

Migration ⓘ

E-cadherin↑, 1, Fibronectin↓, 1, N-cadherin↓, 1, TumCI↓, 1, TumCMig↓, 1, Vim↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, NF-kB↓, 1, PGE2↓, 1,
Total Targets: 10

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: Vim, Vimentin

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#:136  Target#:336  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid