Proanthocyanidins / HK2 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
HK2, Hexokinase 2: Click to Expand ⟱
Source:
Type: enzyme
HK2 (Hexokinase 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. HK2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.
HK2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.
HK2 is a key regulatory enzyme in the glycolytic pathway.
HK2 plays a role in the regulation of glucose metabolism in diabetes.
HK2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.

HK2 Inhibitors:
-2DG
-Curcumin
-Resveratrol
-EGCG
-Berberine
-Methyl Jasmonate (MJ)
-Honokiol
Scientific Papers found: Click to Expand⟱
2396- PACs,    PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma
- in-vitro, HCC, HCCLM3 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2 - in-vitro, Nor, L02
TumCP↓, TumCCA↓, Apoptosis↑, GlucoseCon↓, lactateProd↓, PKM2↓, Glycolysis↓, HK2↓, PFK↓, OXPHOS↑, ChemoSen↑, HSP90↓, Hif1a↓,

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:


Redox & Oxidative Stress ⓘ

OXPHOS↑, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   PFK↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,  

Migration ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: HK2, Hexokinase 2
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#:773  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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