Description: <b>Galloflavin</b> is a flavonoid compound found in certain plants, such as the Galphimia gracilis.
Studies have demonstrated that galloflavin can inhibit the growth of cancer cells and induce apoptosis (cell death) in various types of cancer, including breast, lung, and colon cancer.
Galloflavin's anti-cancer effects are thought to be due to its ability to modulate various cellular signaling pathways, including the PI3K/Akt and NF-κB pathways, which are involved in cell survival and proliferation. Additionally, galloflavin has been shown to have antioxidant and anti-inflammatory properties, which may also contribute to its anti-cancer effects.<br>
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Galloflavin has been reported to be a lactate dehydrogenase (LDH) inhibitor. LDH is an enzyme that plays a crucial role in the metabolism of cancer cells, particularly in the process of glycolysis, which is the breakdown of glucose to produce energy.<br>
Galloflavin's LDH inhibitory activity has been demonstrated in various studies, which have shown that it can inhibit LDH activity in cancer cells, leading to a decrease in lactate production and an increase in the production of reactive oxygen species (ROS). The increase in ROS can lead to cell death, making galloflavin a potential therapeutic agent for the treatment of cancer.<br>
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Galloflavin is unusually clean mechanistically:
-<b>LDH-A inhibition is the primary molecular target</b>
-Everything else (↓ lactate, NAD⁺ stress, ROS, mitochondrial dependence) is downstream
-Apoptosis and tumor suppression are consequences, not drivers
This makes galloflavin one of the best-defined Warburg-effect inhibitors.
Not use if antitumor effect extends to in vivo?
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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>Lactate dehydrogenase (LDH-A and LDH-B)</td>
<td>↓ LDH activity</td>
<td>Warburg glycolysis inhibition</td>
<td>Galloflavin directly inhibits both isoforms of LDH, blocking the conversion of pyruvate to lactate and impairing glycolytic flux in tumor cells. :contentReference[oaicite:1]{index=1}</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/22052811/">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Glycolysis output / ATP synthesis</td>
<td>↓ lactate production & ATP</td>
<td>Reduced cancer cell energy</td>
<td>Galloflavin blocks aerobic glycolysis in multiple tumor cell lines, reducing lactate and ATP, and thus limiting energy available for proliferation. :contentReference[oaicite:2]{index=2}</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/22052811/">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Cell proliferation</td>
<td>↓ proliferation / growth</td>
<td>Growth suppression</td>
<td>Galloflavin inhibits proliferation across several cancer cell models (breast cancer MCF-7, MDA-MB-231, and tamoxifen-resistant cells), independent of glycolytic phenotype. :contentReference[oaicite:3]{index=3}</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/22954722/">(ref)</a></td>
</tr>
<tr>
<td>4</td>
<td>Apoptosis induction</td>
<td>↑ apoptosis (caspase activation)</td>
<td>Programmed cell death</td>
<td>Breast cancer work shows galloflavin induces apoptosis as the main mode of cell death, with signaling differences depending on glycolytic status. :contentReference[oaicite:4]{index=4}</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/22954722/">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>Reactive oxygen species (ROS)</td>
<td>↑ ROS</td>
<td>Oxidative stress</td>
<td>Endometrial cancer cells treated with galloflavin show increased ROS production, potentially contributing to cytotoxicity and DNA damage. :contentReference[oaicite:5]{index=5}</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4316809/">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Mitochondrial apoptosis axis (Bcl-2/MCL-1 changes)</td>
<td>↑ mitochondrial apoptosis</td>
<td>Execution-phase cell death</td>
<td>In endometrial cancer cells, galloflavin increases markers of mitochondrial apoptosis (e.g., cleaved caspase-3) while lowering anti-apoptotic proteins Bcl-2 and Mcl-1. :contentReference[oaicite:6]{index=6}</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4316809/">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>Cell cycle regulation</td>
<td>↑ cell-cycle arrest</td>
<td>Proliferation blockade</td>
<td>GF induces cell-cycle changes in endometrial cancer models (e.g., G2 arrest in some lines), indicating impacts on proliferation checkpoints. :contentReference[oaicite:7]{index=7}</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4316809/">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>Metastasis-related markers (E-cadherin / Slug)</td>
<td>↑ E-cadherin / ↓ Slug</td>
<td>Reduced invasive phenotype</td>
<td>Galloflavin treatment increases E-cadherin and decreases Slug in endometrial cancer cells, consistent with reduced migratory/invasive capacity. :contentReference[oaicite:8]{index=8}</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4316809/">(ref)</a></td>
</tr>
<tr>
<td>9</td>
<td>LDH-A binding to ssDNA & RNA synthesis</td>
<td>↓ LDH-A-ssDNA binding & ↓ RNA synthesis</td>
<td>Transcription/stress axis</td>
<td>Galloflavin prevents LDHA binding to single-stranded DNA and inhibits RNA synthesis independently of glycolysis. :contentReference[oaicite:9]{index=9}</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/23237800/">(ref)</a></td>
</tr>
<tr>
<td>10</td>
<td>Combinatorial metabolic inhibition (in vitro)</td>
<td>↑ metabolic stress when combined</td>
<td>Enhanced anti-proliferative effect</td>
<td>In vitro work shows galloflavin enhances antiproliferative and apoptotic effects in combination with other metabolic inhibitors (e.g., CPI-613) in pancreatic cancer cells. :contentReference[oaicite:10]{index=10}</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266601">(ref)</a></td>
</tr>
</table>