Proanthocyanidins / TumCI 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

TumCI, Tumor Cell invasion: Click to Expand ⟱

Source:

Type:

Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.

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: TumCI, Tumor Cell invasion

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#:324  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid