Description: <b>Chlorogenic acid (CGA)</b> is a polyphenol compound found in various plant-based foods, such as green coffee beans, apples, and pears.<br>
Chlorogenic acid (CGA; 5-caffeoylquinic acid) is a dietary polyphenol (coffee/tea/plant ester) whose primary biology in mammals is redox + stress-response modulation: (1) ROS scavenging/antioxidant buffering, (2) Keap1→NRF2 activation with induction of cytoprotective genes, and (3) downstream anti-inflammatory and survival/metabolic signaling changes (e.g., NF-κB, PI3K/Akt/mTOR/AMPK context-dependent). Oral exposure is PK-limited: after coffee doses, median peak plasma concentrations of CGA-related metabolites are ~1–1.5 µM (1088–1526 nM) , while many in-vitro cancer papers use 10–100+ µM, often exceeding realistic systemic exposure; effects can still be relevant in gut/liver (first-pass) but systemic tumor exposures are likely lower. Clinically, CGA has human PK evidence and extensive preclinical oncology; robust RCT-grade anticancer efficacy is not established, and NRF2 activation creates a credible radio/chemo-resistance risk in some contexts<br>
May lower blood pressure, blood sugar, and weight. May improve mood and cognitive function.
Chlorogenic acid (CGA), one of the most abundant polyphenols in the human diet, has been reported to inhibit cancer cell growth.<br>
• Inhibiting the growth of cancer cells: CGA has been shown to inhibit the growth of cancer cells in vitro and in vivo, including breast, colon, and prostate cancer cells.<br>
• Inducing apoptosis: CGA has been found to induce apoptosis (cell death) in cancer cells, which can help prevent the spread of cancer.<br>
• Reducing inflammation: CGA has anti-inflammatory properties, which can help reduce the risk of cancer by reducing chronic inflammation.<br>
• Antioxidant activity: CGA has antioxidant properties, which can help protect cells from damage caused by free radicals.<br>
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<h3>Chlorogenic Acid (CGA) — Cancer-Relevant Pathway Effects (directional)</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells (↑/↓/↔ + qualifiers)</th>
<th>Normal Cells (↑/↓/↔ + qualifiers)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>ROS / Redox buffering</td>
<td>↓ ROS (often primary; context-dependent)</td>
<td>↓ ROS (protective; often primary)</td>
<td>P–R</td>
<td>Antioxidant/ROS quenching</td>
<td>Can blunt ROS-mediated cytotoxic therapies; shown to reduce radiation-induced ROS/apoptosis in HCC models with ~10 µM pretreatment used in vitro (high vs typical plasma ~1–1.5 µM after coffee). :contentReference[oaicite:2]{index=2}</td>
</tr>
<tr>
<td>2</td>
<td>Keap1 → NRF2 (ARE program)</td>
<td>↑ NRF2 signaling (can promote resistance)</td>
<td>↑ NRF2 signaling (tissue protection)</td>
<td>R–G</td>
<td>Cytoprotective gene induction</td>
<td>In HCC, NRF2 induction/nuclear translocation linked to radioresistance; NRF2 knockdown reversed CGA-mediated protection. NRF2 hyperactivity is a known radio/chemo-resistance axis in cancers. :contentReference[oaicite:3]{index=3}</td>
</tr>
<tr>
<td>3</td>
<td>Radiotherapy interaction (ROS-dependent killing)</td>
<td>↑ radioresistance (model-dependent; NRF2/ROS)</td>
<td>↔ to ↑ protection of normal tissues</td>
<td>P–R</td>
<td>Therapy antagonism risk</td>
<td>Evidence CGA can hinder RT efficacy in some tumor models via ROS scavenging + NRF2 activation. :contentReference[oaicite:4]{index=4}</td>
</tr>
<tr>
<td>4</td>
<td>Inflammation: NF-κB-related signaling</td>
<td>↓ pro-inflammatory signaling (context-dependent)</td>
<td>↓ pro-inflammatory signaling (protective)</td>
<td>R–G</td>
<td>Anti-inflammatory modulation</td>
<td>Commonly reported across CGA-family reviews; may reduce tumor-promoting inflammation but can also reduce immunogenic stress signals depending on context. :contentReference[oaicite:5]{index=5}</td>
</tr>
<tr>
<td>5</td>
<td>PI3K/Akt/mTOR & metabolic stress axes</td>
<td>↓ PI3K/Akt/mTOR (model-/dose-dependent; often high concentration)</td>
<td>↔ / context-dependent</td>
<td>R–G</td>
<td>Anti-proliferative signaling (preclinical)</td>
<td>Frequently claimed in preclinical systems; translational relevance depends on achievable tissue levels and tumor genotype. :contentReference[oaicite:6]{index=6}</td>
</tr>
<tr>
<td>6</td>
<td>Apoptosis / Autophagy balance</td>
<td>↑ apoptosis or ↑ autophagy (model-dependent; often high concentration)</td>
<td>↓ apoptosis under toxic stress (protective)</td>
<td>R–G</td>
<td>Programmed cell-death tuning</td>
<td>Dual-use phenotype: “anticancer” apoptosis claims vs “chemoprotection” in normal tissues. Net effect depends on baseline stress + co-therapy. :contentReference[oaicite:7]{index=7}</td>
</tr>
<tr>
<td>7</td>
<td>Chemo-sensitization vs chemo-protection (adjuvant role)</td>
<td>↔ / mixed (chemo-sensitizing in some models; resistance risk via NRF2 in others)</td>
<td>↑ protection from chemo-toxicity (oxidative/inflammatory injury)</td>
<td>R–G</td>
<td>Adjunct (preclinical)</td>
<td>2024 review frames CGA as potential adjuvant for both overcoming resistance and reducing toxicity, but direction varies by drug/model and redox state. :contentReference[oaicite:8]{index=8}</td>
</tr>
<tr>
<td>8</td>
<td>Ca²⁺ signaling</td>
<td>↔ (not consistently primary)</td>
<td>↔ (not consistently primary)</td>
<td>—</td>
<td>Usually secondary</td>
<td>Ca²⁺ is not a canonical primary axis for CGA in most cancer summaries; include if a specific model ties CGA to ER/mitochondrial Ca²⁺ stress.</td>
</tr>
<tr>
<td>9</td>
<td>Ferroptosis</td>
<td>↔ / context-dependent</td>
<td>↔ / context-dependent</td>
<td>—</td>
<td>Usually secondary</td>
<td>CGA’s dominant profile is antioxidant/NRF2; that generally counters lipid-peroxidation–driven ferroptosis unless paired with pro-oxidant triggers.</td>
</tr>
<tr>
<td>10</td>
<td>Clinical Translation Constraint</td>
<td colspan="2">Systemic tumor exposure likely low; many in-vitro effects require ≥10 µM</td>
<td>—</td>
<td>PK / context risk</td>
<td>Human coffee dosing yields median peak plasma ~1.1–1.5 µM (metabolites); high in-vitro dosing + NRF2-mediated therapy antagonism are key constraints. :contentReference[oaicite:9]{index=9}</td>
</tr>
</table>
<div><b>TSF Legend:</b> P: 0–30 min (primary/rapid effects) R: 30 min–3 hr (acute signaling/stress) G: >3 hr (gene-regulatory adaptation)</div>