Description: <b>An ester</b> formed by the condensation of gallic acid and propanol.<br>
Propyl gallate (PG), chemically known as propyl-3,4,5-trihydroxybenzoate, is widely present in processed food and cosmetics, hair products, and lubricants.<br>
PG alone demonstrated antioxidative and cytoprotective properties against cellular damage and gained a pro-oxidative property in combination with copper (II). It was reported that PG was one of the most active compounds capable of generating H2O2 in DMEM media<br>
<pre>
Main cancer-relevant pathways modulated by propyl gallate
A. Redox imbalance & oxidative stress (dominant)
-↑ Intracellular ROS (context- and dose-dependent)
-Pro-oxidant in cancer cells with high basal ROS
-Mitochondrial superoxide accumulation
-Thiol depletion (↓ GSH, ↓ Trx buffering capacity)
Importance: ★★★★★ (Primary mechanism)
B. Mitochondrial dysfunction & intrinsic apoptosis
-↑ MOMP → caspase cascade
-Loss of mitochondrial membrane potential (ΔΨm)
-Cytochrome-c release
-Caspase-9 → caspase-3 activation
-↑ Bax / ↓ Bcl-2 ratio
Importance: ★★★★☆
C. ER stress & unfolded protein response (UPR)
-↑ PERK–eIF2α–ATF4–CHOP
-ROS-linked protein misfolding
-Pro-apoptotic UPR signaling dominates over adaptive UPR
Importance: ★★★☆☆
D. Cell cycle disruption
-G1 or G2/M arrest (cell-type dependent)
-↓ Cyclin D1, Cyclin B1
-↑ p21, p27
Importance: ★★☆☆☆
E. MAPK stress signaling
-↑ JNK / p38
-Stress-activated apoptosis signaling
-Often precedes mitochondrial failure
Importance: ★★☆☆☆
F. Inflammation & survival pathways (secondary)
-↓ NF-κB, ↓ STAT3 (indirect)
-Suppression is largely ROS-mediated, not direct inhibition
-Reduced anti-apoptotic gene transcription
Importance: ★★☆☆☆
G. NRF2–ARE signaling (dual role)
-Low dose: NRF2 activation → cytoprotection
-High dose / cancer cells: NRF2 overwhelmed → apoptosis
Importance: ★★☆☆☆
(Highly context dependent; double-edged)
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<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>
<tr>
<td>1</td>
<td>Glutathione (GSH) redox buffering</td>
<td>↓ GSH (depletion)</td>
<td>Upstream redox vulnerability</td>
<td>Leukemia and HeLa models report GSH depletion as an early, causal event in PG-induced cytotoxicity</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21112369/">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Nrf2 antioxidant-response axis</td>
<td>↓ Nrf2 nuclear translocation → ↓ γ-GCS</td>
<td>Impaired antioxidant capacity</td>
<td>PG inhibits Nrf2 nuclear translocation and downstream glutathione-synthesis control, linking to GSH depletion and apoptosis in leukemia cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21112369/">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Reactive oxygen species (ROS) balance (context-dependent)</td>
<td>↑ ROS (tumor models) / ↓ ROS (TMZ-combo migration model)</td>
<td>Oxidative-stress modulation</td>
<td>PG increases ROS in hepatocellular carcinoma (HCC) with autophagy/apoptosis; in TMZ-treated glioma, PG inhibits TMZ-induced ROS linked to reduced migration</td>
<td>
<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210513">(ref)</a>
</td>
</tr>
<tr>
<td>4</td>
<td>MAPK stress signaling (ERK/JNK/p38)</td>
<td>↑ MAPK activation</td>
<td>Stress-to-death signaling</td>
<td>PG activates MAPKs; authors position MAPKs/Nrf2-mediated GSH depletion as an early driver of apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21112369/">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>Autophagy program (LC3 conversion)</td>
<td>↑ autophagy</td>
<td>Stress response contributing to growth inhibition</td>
<td>HCC study: PG induces ROS and activates autophagy (LC3-I→LC3-II), with associated apoptosis markers</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210513">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Apoptosis (caspase cascade; intrinsic/extrinsic components)</td>
<td>↑ caspase activation / ↑ apoptosis</td>
<td>Programmed cell death</td>
<td>Leukemia: caspases-3/8/9 activation with p53/Bax/Fas/FasL changes; lung cancer: caspase-dependent apoptosis with PARP cleavage</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21112369/">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>Cell-cycle regulation</td>
<td>↑ G1 arrest (e.g., ↑ p27)</td>
<td>Proliferation blockade</td>
<td>HeLa and lung cancer models report PG-induced G1 phase arrest with cell-cycle regulator changes</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20204304/">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>Lung cancer growth suppression</td>
<td>↓ proliferation / ↓ viability</td>
<td>Anti-growth effect</td>
<td>PG reduces growth of Calu-6 and A549 lung cancer cells with G1 arrest and caspase-dependent apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/33125113/">(ref)</a></td>
</tr>
<tr>
<td>9</td>
<td>Migration / invasion phenotype (TMZ-combination glioma model)</td>
<td>↓ migration (via ↓ TMZ-induced ROS; NF-κB pathway implicated in full paper title)</td>
<td>Anti-migratory effect (combination context)</td>
<td>TMZ + PG enhances inhibition of U87MG glioma migration; abstract states PG inhibits TMZ-induced ROS and implicates mitochondrial complex III / NADPH oxidase as ROS sources</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/29062841/">(ref)</a></td>
</tr>
<tr>
<td>10</td>
<td>In vivo anti-tumor effect (HCC; zebrafish model)</td>
<td>↓ tumor growth / ↓ proliferation</td>
<td>Demonstrated in vivo activity</td>
<td>HCC study includes in vivo suppression (zebrafish) alongside ROS increase and autophagy activation</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210513">(ref)</a></td>
</tr>
</table>