Description: <b>Grapeseed extract (GSE)</b> 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.
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Made from seeds of grapes and contains antioxidants Vitamin E, linolenic acid and OPCs.<br>
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<h3>Cancer Pathway Table: Grapeseed Extract</h3>
<!-- Cancer Pathway Table: Grapeseed Extract -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB inflammatory / survival signaling</td>
<td>NF-κB ↓; COX-2 ↓; cytokines ↓ (reported)</td>
<td>Inflammatory tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory / anti-survival</td>
<td>Consistent suppression of inflammatory signaling in multiple tumor models.</td>
</tr>
<tr>
<td>2</td>
<td>PI3K → AKT → mTOR axis</td>
<td>PI3K/AKT ↓; proliferation ↓ (model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth signaling suppression</td>
<td>Frequently reported mechanism contributing to reduced tumor growth.</td>
</tr>
<tr>
<td>3</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>Bax ↑; Bcl-2 ↓; caspases ↑ (reported)</td>
<td>Minimal apoptosis at lower exposure</td>
<td>G</td>
<td>Apoptotic induction</td>
<td>Apoptosis induction associated with mitochondrial depolarization and cytochrome c release.</td>
</tr>
<tr>
<td>4</td>
<td>Cell-cycle arrest (G1 / G2-M)</td>
<td>Cell-cycle arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often linked to decreased Cyclin D1/CDK expression.</td>
</tr>
<tr>
<td>5</td>
<td>ROS modulation (biphasic)</td>
<td>ROS ↑ in some tumor contexts; apoptosis ↑</td>
<td>ROS ↓; antioxidant protection</td>
<td>P, R</td>
<td>Redox modulation</td>
<td>Polyphenol-rich extracts may act antioxidant in normal cells and pro-oxidant in tumor cells at higher doses.</td>
</tr>
<tr>
<td>6</td>
<td>Nrf2 / ARE pathway</td>
<td>Context-dependent modulation</td>
<td>Nrf2 ↑; antioxidant enzyme expression ↑</td>
<td>R, G</td>
<td>Redox regulation</td>
<td>Common polyphenol signature; may protect normal tissue during oxidative stress.</td>
</tr>
<tr>
<td>7</td>
<td>MAPK signaling (ERK / JNK / p38)</td>
<td>Stress-MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>JNK/p38 activation linked to apoptosis; ERK modulation varies.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis (VEGF signaling)</td>
<td>VEGF ↓; angiogenesis ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic</td>
<td>Anti-angiogenic activity observed in several preclinical systems.</td>
</tr>
<tr>
<td>9</td>
<td>Metastasis / invasion (MMPs)</td>
<td>MMP2/MMP9 ↓; migration ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Likely downstream of NF-κB and MAPK suppression.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability constraint</td>
<td>Systemic exposure limited; metabolite-driven effects</td>
<td>Generally well tolerated</td>
<td>—</td>
<td>Translation constraint</td>
<td>OPCs have limited oral bioavailability; many in vitro concentrations exceed typical plasma levels.</td>
</tr>
</table>
<p><small>
TSF: P = rapid redox effects; R = signaling pathway modulation; G = apoptosis, angiogenesis, and phenotype-level changes.
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