tbResList Print — ART/DHA Artemisinin

Description: <b>Artemisinin</b> a compound in a Chinese herb that may inhibit tumor growth and metastasis
Artemisinin (antimalarial drugs)<br>
Artesunic acid (Artesunate) , Dihydroartemisinin (DHA), artesunate, arteether, and artemether, SM735, SM905, SM933, SM934, and SM1044 <br>
<br>
The induction of OS in tumor cells via the production of ROS is the key mechanism of ART against cancer.<br>
combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.<br>
<br>
Summary:<br>
- One of the strongest tumor-selective pro-oxidants, mechanism related with iron. Synergizes with iron-rich tumors<br>
-<a href="tbResList.php?qv=34&tsv=275&wNotes=on">ROS</a> seems to affect both cancer and normal cells<br>
- Delivery of <a href="tbResEdit.php?rid=2577">
artemisinin in conjugate form with transferrin</a> or holotransferrin (serum iron transport proteins) have been shown to greatly improve its effectiveness.<br>
- Potential direct inhibitor of
<a href="tbResList.php?qv=34&tsv=373&wNotes=on&exSp=open">STAT3 </a><br>
- <a href="tbResList.php?qv=34&qv2=19&wNotes=on&exSp=open">
Artemisinin synergized with the glycolysis inhibitor 2DG</a> (2-deoxy- D -glucose)<br>
ART Combined Therapy:
<a href="tbResList.php?qv=34&qv2=27&wNotes=on&exSp=open">Allicin</a>,
<a href="tbResList.php?qv=34&qv2=141&wNotes=on&exSp=open">Resveratrol</a>,
<a href="tbResList.php?qv=34&qv2=65&wNotes=on&exSp=open">Curcumin</a>,
<a href="tbResList.php?qv=34&qv2=166&wNotes=on&exSp=open">VitC</a> (but not orally at same time),
<a href="tbResList.php?qv=34&qv2=15&wNotes=on&exSp=open">Butyrate </a>,
<a href="tbResList.php?qv=34&qv2=19&wNotes=on&exSp=open">2-DG</a>,
<a href="tbResList.php?qv=34&qv2=332&wNotes=on&exSp=open">Aminolevulinic AcidG</a>
<br>
-possible problems with <a href="tbResEdit.php?rid=2571">liver toxicity??</a><br>
<br>
-Artesunate (ART), an artemisinin compound, is known for lysosomal degradation of ferritin, inducing oxidative stress and promoting cancer cell death.<br>

<br>
Pathways:<br>
- Increasing reactive oxygen species (ROS) production. This oxidative stress can cause the loss of mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspase cascades.<br>
- Downregulate HIF-1α<br>
- By impairing glycolysis, artemisinin might force cells to rely on oxidative phosphorylation (OXPHOS) for energy production.<br>
- Inhibit GLUT1 (glucose uptake), HK2, PKM2 (slow the glycolytic flux, thereby reducing the energy supply)<br>
- Minimal NRF2 activation<br>
<br>

-Artemisinin has a <a href="tbResList.php?qv=34&&tsv=1109&wNotes=on&exSp=open">half-life </a> of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hour.<br>
<a href="tbResList.php?qv=34&tsv=792&wNotes=on&exSp=open">BioAv</a> 21%, poor-good solubility. Artesunate (ART), a water soluble derivative of artemisinin. concentrations higher in blood, colon, liver, kidney (highly perfused organs)
<br>
Pathways:<br>

<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- induce
<a href="tbResList.php?qv=34&tsv=275&wNotes=on">ROS</a> production, iron dependent (affect both cancer and normal cells)<br>
- ROS↑ related:
<a href="tbResList.php?qv=34&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?qv=34&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?qv=34&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?qv=34&tsv=356&wNotes=on">GRP78↑</a>,
<a href="tbResList.php?qv=34&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?qv=34&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?qv=34&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?qv=34&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=HSP">HSP↓</a>,
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=Prx">Prx</a>,--><!-- mitochondrial antioxidant enzyme-->

<br>

<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Both Lowers (and raises) AntiOxidant defense in Cancer Cells:
<a href="tbResList.php?qv=34&tsv=226&wNotes=on&word=NRF2">NRF2↓</a>(contary),
<!-- <a href="tbResList.php?qv=34&word=Trx&wNotes=on">TrxR↓**</a>, --><!-- major antioxidant system -->
<a href="tbResList.php?qv=34&tsv=298&wNotes=on&word=SOD↓">SOD↓</a>,
<a href="tbResList.php?qv=34&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<a href="tbResList.php?qv=34&tsv=46&wNotes=on">Catalase↓</a>
<!-- <a href="tbResList.php?qv=34&tsv=597&wNotes=on">HO1↓</a> -->
<a href="tbResList.php?qv=34&wNotes=on&word=GPx">GPx↓</a>


<br>

- Small evidence of Raising
<a href="tbResList.php?qv=34&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?qv=34&tsv=275&wNotes=on&word=ROS">ROS↓</a>(contary),
<a href="tbResList.php?qv=34&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?qv=34&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>(contary),
<a href="tbResList.php?qv=34&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?qv=34&tsv=46&wNotes=on&word=Catalase↑">Catalase↑</a>,
<br>

<!-- INFLAMMATION : NF-kB↓, COX2↓, COX2↓ PRO-INFL CYTOKINES: IL-1β↓, TNF-α↓, IL-6↓, IL-8↓, -->
- lowers
<a href="tbResList.php?qv=34&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?qv=34&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?qv=34&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?qv=34&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?qv=34&tsv=908&wNotes=on&word=NLRP3↓">NLRP3↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>, -->
<a href="tbResList.php?qv=34&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?qv=34&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?qv=34&tsv=368&wNotes=on&word=IL8↓">IL-8↓</a>
<br>



<!-- GROWTH/METASTASES : EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1, uPA↓, VEGF↓, ERK↓
inhibiting metastasis-associated proteins such as ROCK1, FAK, (RhoA), NF-κB and u-PA, MMP-1 and MMP-13.-->
- inhibit Growth/Metastases :
<a href="tbResList.php?qv=34&tsv=604&wNotes=on">TumMeta↓</a>,
<a href="tbResList.php?qv=34&tsv=323&wNotes=on">TumCG↓</a>,
<a href="tbResList.php?qv=34&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=34&tsv=204&wNotes=on">MMPs↓</a>,
<a href="tbResList.php?qv=34&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?qv=34&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?qv=34&tsv=308&wNotes=on">TIMP2</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=IGF">IGF-1↓</a>,
<a href="tbResList.php?qv=34&tsv=428&wNotes=on">uPA↓</a>,
<a href="tbResList.php?qv=34&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=34&tsv=1284&wNotes=on">ROCK1↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=110&wNotes=on">FAK↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=273&wNotes=on">RhoA↓</a>, -->
<a href="tbResList.php?qv=34&tsv=214&wNotes=on">NF-κB↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=79&wNotes=on">CXCR4↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=1247&wNotes=on">SDF1↓</a>, -->
<a href="tbResList.php?qv=34&tsv=304&wNotes=on">TGF-β↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=719&wNotes=on">α-SMA↓</a>, -->
<a href="tbResList.php?qv=34&tsv=105&wNotes=on">ERK↓</a>
<!-- <a href="tbResList.php?qv=34&tsv=1178&wNotes=on">MARK4↓</a> --><!-- contributing to tumor growth, invasion, and metastasis-->
<br>

<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
<!--
- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=34&tsv=140&wNotes=on">HDAC↓</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=DNMT">DNMTs↓</a>,
<a href="tbResList.php?qv=34&tsv=108&wNotes=on">EZH2↓</a>,
<a href="tbResList.php?qv=34&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=HSP">HSP↓</a>,
<a href="tbResList.php?qv=34&tsv=506&wNotes=on">Sp proteins↓</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=TET">TET↑</a>
<br> -->

<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?qv=34&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?qv=34&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?qv=34&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?qv=34&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?qv=34&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?qv=34&tsv=895&wNotes=on">CDK6↓</a>,
<br>

<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?qv=34&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?qv=34&tsv=324&wNotes=on">TumCI↓</a>,
<a href="tbResList.php?qv=34&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>, <!-- encourages invasion, proliferation, EMT, and angiogenesis -->
<!-- <a href="tbResList.php?qv=34&tsv=110&wNotes=on">FAK↓</a>, -->
<a href="tbResList.php?qv=34&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=34&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=TOP">TOP1↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=657&wNotes=on">TET1</a>, -->
<br>

<!-- GLYCOLYSIS : ATP↓, HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓, lactateProd, OXPHOS -->
- inhibits
<a href="tbResList.php?qv=34&tsv=129&wNotes=on">glycolysis</a>
/<a href="tbResList.php?qv=34&tsv=947&wNotes=on">Warburg Effect</a> and
<a href="tbResList.php?qv=34&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?qv=34&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?qv=34&tsv=772&wNotes=on">PKM2↓</a>,
<a href="tbResList.php?qv=34&tsv=35&wNotes=on">cMyc↓</a>,
<a href="tbResList.php?qv=34&tsv=566&wNotes=on&word=GLUT">GLUT1↓</a>,
<a href="tbResList.php?qv=34&tsv=906&wNotes=on">LDH↓</a>,
<a href="tbResList.php?qv=34&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<a href="tbResList.php?qv=34&tsv=773&wNotes=on">HK2↓</a>,
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=PFK">PFKs↓</a>, -->
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=PDK">PDKs↓</a>, -->
<a href="tbResList.php?qv=34&tsv=847&wNotes=on">ECAR↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=230&wNotes=on">OXPHOS↓</a>, -->
<a href="tbResList.php?qv=34&tsv=356&wNotes=on">GRP78↑</a>,
<!-- <a href="tbResList.php?qv=34&tsv=1278&wNotes=on">Glucose↓</a>, -->
<a href="tbResList.php?qv=34&tsv=623&wNotes=on">GlucoseCon↓</a>
<br>


<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=34&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=34&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=34&tsv=143&wNotes=on">HIF-1α↓</a>,
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=NOTCH">Notch↓</a>, -->
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=FGF">FGF↓</a>, -->
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=PDGF">PDGF↓</a>, -->
<a href="tbResList.php?qv=34&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<a href="tbResList.php?qv=34&&wNotes=on&word=ITG">Integrins↓</a>,
<br>

<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- some small indication of inhibiting Cancer Stem Cells :
<a href="tbResList.php?qv=34&tsv=795&wNotes=on">CSC↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=524&wNotes=on">CK2↓</a>, -->
<a href="tbResList.php?qv=34&tsv=141&wNotes=on">Hh↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=434&wNotes=on">GLi↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=124&wNotes=on">GLi1↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=677&wNotes=on">CD133↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=655&wNotes=on">CD24↓</a>, -->
<a href="tbResList.php?qv=34&tsv=342&wNotes=on">β-catenin↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=357&wNotes=on">n-myc↓</a>, -->
<a href="tbResList.php?qv=34&tsv=656&wNotes=on">sox2↓</a>,
<!-- <a href="tbResList.php?qv=34&wNotes=on&word=NOTCH">Notch2↓</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=1024&wNotes=on">nestin↓</a>, -->
<a href="tbResList.php?qv=34&tsv=508&wNotes=on">OCT4↓</a>,
<br>

<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=34&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=34&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=JAK">JAK↓</a>,
<a href="tbResList.php?qv=34&wNotes=on&word=STAT">STAT↓</a>,
<a href="tbResList.php?qv=34&tsv=377&wNotes=on">Wnt↓</a>,
<a href="tbResList.php?qv=34&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=34&tsv=9&wNotes=on">AMPK</a>,
<!-- <a href="tbResList.php?qv=34&tsv=475&wNotes=on">α↓</a>, -->
<a href="tbResList.php?qv=34&tsv=105&wNotes=on">ERK↓</a>,
<!-- <a href="tbResList.php?qv=34&tsv=1014&wNotes=on">5↓</a>, -->
<a href="tbResList.php?qv=34&tsv=168&wNotes=on">JNK</a>,


<!-- - <a href="tbResList.php?qv=34&wNotes=on&word=SREBP">SREBP</a> (related to cholesterol). -->
<br>


<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=34&tsv=1106&wNotes=on">chemo-sensitization</a>,
<!-- <a href="tbResList.php?qv=34&tsv=1171&wNotes=on">chemoProtective</a>, -->
<a href="tbResList.php?qv=34&tsv=1107&wNotes=on">RadioSensitizer</a>,
<!-- <a href="tbResList.php?qv=34&tsv=1185&wNotes=on">RadioProtective</a>, -->
<a href="tbResList.php?qv=34&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<!-- <a href="tbResList.php?qv=34&tsv=1105&wNotes=on">Neuroprotective</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=557&wNotes=on">Cognitive</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=1175&wNotes=on">Renoprotection</a>, -->
<!-- <a href="tbResList.php?qv=34&tsv=1179&wNotes=on">Hepatoprotective</a>, -->
<!-- <a href="tbResList.php?&qv=34&tsv=1188&wNotes=on">CardioProtective</a>, -->

<br>
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=34&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
<br>
Often synergistic with ROS-based chemo<br>
<br>


<table>
<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>Iron-activated endoperoxide chemistry (radical formation)</td>
<td>↑ carbon-centered radicals (iron-dependent activation)</td>
<td>Primary cytotoxic trigger</td>
<td>Artemisinin-class endoperoxides generate carbon-centered radicals that drive downstream cytotoxicity (mechanistic chemical evidence)</td>
<td><a href="https://www.jbc.org/article/S0021-9258%2819%2933590-2/fulltext" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>ROS accumulation</td>
<td>↑ ROS</td>
<td>Oxidative stress overload</td>
<td>DHA induces cytotoxicity associated with ROS overproduction; ROS accompanies mitochondrial dysfunction in cancer cells</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5651661/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓ ΔΨm</td>
<td>Mitochondrial dysfunction</td>
<td>DHA decreases mitochondrial membrane potential during intrinsic apoptotic progression in cancer cells</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2653522/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>↑ caspase-3 activation</td>
<td>Programmed cell death</td>
<td>DHA induces apoptosis via a caspase-3–dependent mitochondrial death pathway (lung adenocarcinoma model)</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2653522/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>Ferroptosis (iron-dependent lipid peroxidation)</td>
<td>↑ ferroptosis</td>
<td>Non-apoptotic oxidative death modality</td>
<td>Demonstrates DHA initiates ferroptosis with lipid peroxide readouts and ferroptosis-inhibitor rescue (glioblastoma context)</td>
<td><a href="https://portlandpress.com/bioscirep/article/40/6/BSR20193314/225000/Dihydroartemisinin-initiates-ferroptosis-in" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>Transferrin receptor / iron uptake dependence</td>
<td>↑ dependence on TfR1 axis</td>
<td>Iron-selective vulnerability</td>
<td>DHA anticancer activity is linked to regulation/usage of cell-surface transferrin receptor-1 in cancer cells</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042703" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>ER stress / UPR (GRP78, CHOP, eIF2α)</td>
<td>↑ ER stress markers</td>
<td>Proteotoxic stress apoptosis signaling</td>
<td>DHA induces ER-stress pathway engagement (GRP78, CHOP, eIF2α) alongside mitochondrial apoptosis features</td>
<td><a href="https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00310/full" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>Autophagy (stress-induced program)</td>
<td>↑ autophagy</td>
<td>Adaptive or pro-death response</td>
<td>DHA stimulates autophagy through repression of NF-κB activity (autophagy induction direction shown)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24099910/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>PI3K–AKT–mTOR survival signaling</td>
<td>↓ mTORC1 signaling</td>
<td>Reduced growth &amp; survival signaling</td>
<td>DHA inhibits mTORC1 signaling (mechanism shown via AMPK activation) in tumor cells</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8226784/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB nuclear translocation</td>
<td>Reduced pro-survival / inflammatory transcription</td>
<td>DHA blocks NF-κB p65 nuclear translocation and links this to VEGFR2 regulation in endothelial/angiogenesis context</td>
<td><a href="https://www.tandfonline.com/doi/full/10.4161/15384047.2014.955728" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>Cell cycle control</td>
<td>↑ G2/M arrest</td>
<td>Proliferation blockade</td>
<td>DHA shows anticancer effect through autophagy-dependent cell cycle arrest at the G2/M phase (esophageal cancer model)</td>
<td><a href="https://link.springer.com/article/10.1186/s13020-020-00318-w" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>Angiogenesis signaling (VEGFR2 axis)</td>
<td>↓ VEGFR2 signaling</td>
<td>Anti-angiogenic effect</td>
<td>Directly reports DHA targets VEGFR2 via NF-κB pathway modulation, consistent with anti-angiogenic activity</td>
<td><a href="https://www.tandfonline.com/doi/full/10.4161/15384047.2014.955728" target="_blank">(ref)</a></td>
</tr>

</table>