Description: <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5429338/"> <b>"Anthocyanins</b> are a class of water‐soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti‐inflammation; anti‐mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti‐invasion; anti‐metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy." </a> <br>
Anthocyanins are flavonoid pigments with multi-target pleiotropic effects in cancer models, primarily through modulation of ROS balance, NF-κB signaling, PI3K/Akt/mTOR inhibition, apoptosis induction, and anti-angiogenic activity. Their effects are often context-dependent and dose-dependent: low physiologic exposures tend to support antioxidant and anti-inflammatory tone, whereas higher concentrations in vitro can induce oxidative stress and apoptosis in tumor cells. They also influence tumor microenvironment dynamics including VEGF signaling, MMP activity, and inflammatory cytokines. Bioavailability is modest, and metabolites (phenolic acids) likely contribute significantly to biological effects. Evidence in humans remains supportive but not definitive.<br>
• Anthocyanins are a class of water-soluble flavonoid pigments responsible for the red, purple, and blue hues in many fruits, vegetables, and flowers (e.g., berries, red grapes, and eggplants). <br>
• Anthocyanins can effectively scavenge free radicals and reduce oxidative stress, thereby protecting cellular components like DNA, lipids, and proteins from oxidative damage—a factor linked to carcinogenesis. <br>
• Their antioxidant capacity helps in neutralizing reactive oxygen species (ROS), which can otherwise promote mutations and tumor initiation. <br>
• Anthocyanins have been shown to inhibit pro-inflammatory cytokines (e.g., TNF-α, IL-6) and enzymes (e.g., COX-2), reducing the inflammatory signals associated with cancer progression. <br>
• They may modulate pathways such as NF-κB, MAPK, and PI3K/Akt, contributing to the downregulation of genes involved in survival and proliferation of cancer cells. <br>
• Anthocyanins have been found to inhibit the formation of new blood vessels (angiogenesis) essential for tumor growth and metastatic spread. <br>
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<h3>Anthocyanins – Cancer Pathway Matrix</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Direction</th>
<th>Mechanism Snapshot</th>
<th>TSF</th>
<th>Evidence</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB Signaling</td>
<td>NF-κB ↓</td>
<td>Suppresses inflammatory transcription signaling → cytokines ↓ (IL-6, TNF-α)</td>
<td>R, G</td>
<td>Preclinical strong</td>
<td>Core anti-inflammatory anti-tumor mechanism; reduces pro-survival signaling.</td>
</tr>
<tr>
<td>2</td>
<td>PI3K/Akt/mTOR Axis</td>
<td>Akt ↓, mTOR ↓</td>
<td>Downregulates proliferative and survival pathways</td>
<td>R, G</td>
<td>Preclinical strong</td>
<td>Common across breast, colon, liver, prostate models.</td>
</tr>
<tr>
<td>3</td>
<td>Apoptosis (Intrinsic)</td>
<td>Caspase ↑, Bcl-2 ↓</td>
<td>Modulates mitochondrial membrane potential → cytochrome c release</td>
<td>R, G</td>
<td>Preclinical strong</td>
<td>Often secondary to ROS modulation or Akt inhibition.</td>
</tr>
<tr>
<td>4</td>
<td>ROS Modulation (Biphasic)</td>
<td>ROS ↑ (tumor, high dose)<br>ROS ↓ (normal tissue)</td>
<td>Antioxidant at low dose; pro-oxidant stress in tumor at higher concentrations</td>
<td>P, R</td>
<td>Preclinical strong</td>
<td>Context-dependent; redox-selective effects reported.</td>
</tr>
<tr>
<td>5</td>
<td>Angiogenesis (VEGF)</td>
<td>VEGF ↓</td>
<td>Inhibits VEGF expression and endothelial migration</td>
<td>G</td>
<td>Preclinical moderate</td>
<td>Anti-angiogenic effect supports tumor growth restriction.</td>
</tr>
<tr>
<td>6</td>
<td>MMPs / Metastasis</td>
<td>MMP-2 ↓, MMP-9 ↓</td>
<td>Suppresses extracellular matrix degradation</td>
<td>G</td>
<td>Preclinical moderate</td>
<td>Reduces invasion and metastatic behavior in models.</td>
</tr>
<tr>
<td>7</td>
<td>Cell Cycle Regulation</td>
<td>G1/S arrest</td>
<td>Modulates cyclins and CDKs</td>
<td>R</td>
<td>Preclinical moderate</td>
<td>Often coordinated with Akt/NF-κB suppression.</td>
</tr>
<tr>
<td>8</td>
<td>HIF-1α / Hypoxia</td>
<td>HIF-1α ↓</td>
<td>Reduces hypoxia-driven glycolytic gene expression</td>
<td>G</td>
<td>Preclinical emerging</td>
<td>Links to Warburg metabolism modulation.</td>
</tr>
<tr>
<td>9</td>
<td>Nrf2 Pathway</td>
<td>Nrf2 ↑ (normal)<br>Variable in tumor</td>
<td>Induces antioxidant response genes</td>
<td>R, G</td>
<td>Preclinical mixed</td>
<td>Protective in normal tissue; theoretical caution in Nrf2-addicted tumors.</td>
</tr>
</table>
<p><strong>Time-Scale Flag (TSF):</strong><br>
P = 0–30 min (direct redox interactions)<br>
R = 30 min–3 hr (signal transduction shifts)<br>
G = >3 hr (gene expression, apoptosis, angiogenesis modulation)</p>