tbResList Print — SK Shikonin

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Product

SK Shikonin
Description: <b>The (R)-enantiomer of alkannin</b> is known as shikonin, and the racemic mixture of the two is known as shikalkin.<br>
Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon). <br>
Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao'<br>
-Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties<br>
-Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin<br>
-ic50 cancer cells 1-10uM, normal cells >10uM<br>
<br>

-known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway)<br>

<br>
Available from <a href="https://www.mcsformulas.com/" > mcsformulas.com </a>
Shikonin Pro Liposomal, 30 mg<br>
Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin)<br>


<br>
-Note <a href="tbResList.php?qv=150&tsv=1109&wNotes=on&exSp=open">half-life</a>15-30mins or 8hr?.<br>
<a href="tbResList.php?qv=150&tsv=792&wNotes=on&exSp=open">BioAv</a> low, poor water solubility
<br>
Pathways:<br>

<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- usually induce
<a href="tbResList.php?qv=150&tsv=275&wNotes=on">ROS</a> production in cancer cells, and reduce ROS in normal cells.<br>
- ROS↑ related:
<a href="tbResList.php?qv=150&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?qv=150&tsv=103&wNotes=on">ER Stress↑</a>,
<!--<a href="tbResList.php?qv=150&tsv=459&wNotes=on">UPR↑</a>, -->
<a href="tbResList.php?qv=150&tsv=356&wNotes=on">GRP78↑</a>,
<a href="tbResList.php?qv=150&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?qv=150&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?qv=150&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?qv=150&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=HSP">HSP↓</a>,
<!--<a href="tbResList.php?qv=150&wNotes=on&word=Prx">Prx</a>, --><!-- mitochondrial antioxidant enzyme-->

<br>

<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Lowers AntiOxidant defense in Cancer Cells:
<a href="tbResList.php?qv=150&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?qv=150&word=Trx&wNotes=on">TrxR↓**</a>,<!-- major antioxidant system -->
<a href="tbResList.php?qv=150&tsv=298&wNotes=on&word=SOD↓">SOD↓</a>,
<a href="tbResList.php?qv=150&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<a href="tbResList.php?qv=150&tsv=46&wNotes=on">Catalase↓</a>
<!-- <a href="tbResList.php?qv=150&tsv=597&wNotes=on">HO1↓</a> -->
<a href="tbResList.php?qv=150&wNotes=on&word=GPx">GPx4↓</a>


<br>

- Raises
<a href="tbResList.php?qv=150&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?qv=150&tsv=275&wNotes=on&word=ROS↓">ROS↓</a>,
<a href="tbResList.php?qv=150&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?qv=150&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?qv=150&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?qv=150&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=150&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?qv=150&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?qv=150&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?qv=150&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?qv=150&tsv=908&wNotes=on&word=NLRP3↓">NLRP3↓</a>,
<a href="tbResList.php?qv=150&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?qv=150&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?qv=150&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?qv=150&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=150&tsv=604&wNotes=on">TumMeta↓</a>,
<a href="tbResList.php?qv=150&tsv=323&wNotes=on">TumCG↓</a>,
<a href="tbResList.php?qv=150&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=150&tsv=204&wNotes=on">MMPs↓</a>,
<a href="tbResList.php?qv=150&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?qv=150&tsv=203&wNotes=on">MMP9↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=308&wNotes=on">TIMP2</a>, -->
<a href="tbResList.php?qv=150&tsv=415&wNotes=on">IGF-1↓</a>,
<a href="tbResList.php?qv=150&tsv=428&wNotes=on">uPA↓</a>,
<a href="tbResList.php?qv=150&tsv=334&wNotes=on">VEGF↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=1284&wNotes=on">ROCK1↓</a>, -->
<a href="tbResList.php?qv=150&tsv=110&wNotes=on">FAK↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=273&wNotes=on">RhoA↓</a>, -->
<a href="tbResList.php?qv=150&tsv=214&wNotes=on">NF-κB↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=79&wNotes=on">CXCR4↓</a>, -->
<!-- <a href="tbResList.php?qv=150&tsv=1247&wNotes=on">SDF1↓</a>, -->
<a href="tbResList.php?qv=150&tsv=304&wNotes=on">TGF-β↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=719&wNotes=on">α-SMA↓</a>, -->
<a href="tbResList.php?qv=150&tsv=105&wNotes=on">ERK↓</a>
<!-- <a href="tbResList.php?qv=150&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=150&tsv=140&wNotes=on">HDAC↓</a>,
<a href="tbResList.php?qv=150&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=150&tsv=86&wNotes=on">DNMT3A↓</a>,
<a href="tbResList.php?qv=150&tsv=108&wNotes=on">EZH2↓</a>,
<a href="tbResList.php?qv=150&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=HSP">HSP↓</a>,
<a href="tbResList.php?qv=150&tsv=506&wNotes=on">Sp proteins↓</a>,

<br> -->

<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?qv=150&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?qv=150&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?qv=150&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?qv=150&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?qv=150&tsv=894&wNotes=on">CDK4↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=895&wNotes=on">CDK6↓</a>, -->
<br>

<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?qv=150&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?qv=150&tsv=324&wNotes=on">TumCI↓</a>,
<a href="tbResList.php?qv=150&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?qv=150&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=150&tsv=96&wNotes=on">EMT↓</a>,
<!-- <a href="tbResList.php?qv=150&tsv=1117&wNotes=on">TOP1↓</a>, -->
<!-- <a href="tbResList.php?qv=150&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=150&tsv=129&wNotes=on">glycolysis</a>
/<a href="tbResList.php?qv=150&tsv=947&wNotes=on">Warburg Effect</a> and
<a href="tbResList.php?qv=150&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?qv=150&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?qv=150&tsv=772&wNotes=on">PKM2↓</a>,
<a href="tbResList.php?qv=150&tsv=35&wNotes=on">cMyc↓</a>,
<a href="tbResList.php?qv=150&tsv=566&wNotes=on&word=GLUT">GLUT1↓</a>,
<a href="tbResList.php?qv=150&tsv=906&wNotes=on">LDH↓</a>,
<a href="tbResList.php?qv=150&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<a href="tbResList.php?qv=150&tsv=773&wNotes=on">HK2↓</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=PFK">PFKs↓</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=PDK">PDKs↓</a>,
<a href="tbResList.php?qv=150&tsv=847&wNotes=on">ECAR↓</a>,
<a href="tbResList.php?qv=150&tsv=230&wNotes=on">OXPHOS↓</a>,
<a href="tbResList.php?qv=150&tsv=356&wNotes=on">GRP78↑</a>,
<!-- <a href="tbResList.php?qv=150&tsv=1278&wNotes=on">Glucose↓</a>, -->
<a href="tbResList.php?qv=150&tsv=623&wNotes=on">GlucoseCon↓</a>
<br>


<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=150&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=150&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=150&tsv=143&wNotes=on">HIF-1α↓</a>,
<!-- <a href="tbResList.php?qv=150&wNotes=on&word=NOTCH">Notch↓</a>, -->
<!-- <a href="tbResList.php?qv=150&wNotes=on&word=FGF">FGF↓</a>, -->
<!-- <a href="tbResList.php?qv=150&tsv=361&wNotes=on">PDGF↓</a>, -->
<a href="tbResList.php?qv=150&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<a href="tbResList.php?qv=150&&wNotes=on&word=ITG">Integrins↓</a>,
<br>

<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
<!--
- inhibits Cancer Stem Cells :
<a href="tbResList.php?qv=150&tsv=795&wNotes=on">CSC↓</a>,
<a href="tbResList.php?qv=150&tsv=524&wNotes=on">CK2↓</a>,
<a href="tbResList.php?qv=150&tsv=141&wNotes=on">Hh↓</a>,
<a href="tbResList.php?qv=150&tsv=434&wNotes=on">GLi↓</a>,
<a href="tbResList.php?qv=150&tsv=124&wNotes=on">GLi1↓</a>,
<a href="tbResList.php?qv=150&tsv=677&wNotes=on">CD133↓</a>,
<a href="tbResList.php?qv=150&tsv=655&wNotes=on">CD24↓</a>,
<a href="tbResList.php?qv=150&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=150&tsv=357&wNotes=on">n-myc↓</a>,
<a href="tbResList.php?qv=150&tsv=656&wNotes=on">sox2↓</a>,
<a href="tbResList.php?qv=150&tsv=222&wNotes=on">notch2↓</a>,
<a href="tbResList.php?qv=150&tsv=1024&wNotes=on">nestin↓</a>,
<a href="tbResList.php?qv=150&tsv=508&wNotes=on">OCT4↓</a>,
<br>
-->

<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=150&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=150&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=JAK">JAK↓</a>,
<a href="tbResList.php?qv=150&wNotes=on&word=STAT">STAT↓</a>,
<!--<a href="tbResList.php?qv=150&tsv=377&wNotes=on">Wnt↓</a>, -->
<a href="tbResList.php?qv=150&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=150&tsv=9&wNotes=on">AMPK</a>,
<!--<a href="tbResList.php?qv=150&tsv=475&wNotes=on">α↓</a>, -->
<a href="tbResList.php?qv=150&tsv=105&wNotes=on">ERK↓</a>,
<!--<a href="tbResList.php?qv=150&tsv=1014&wNotes=on">5↓</a>, -->
<a href="tbResList.php?qv=150&tsv=168&wNotes=on">JNK</a>,
<a href="tbResList.php?qv=150&tsv=236&wNotes=on">P53↑</a>,
<br>


<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=150&tsv=1106&wNotes=on">chemo-sensitization</a>,
<a href="tbResList.php?qv=150&tsv=1171&wNotes=on">chemoProtective</a>,
<a href="tbResList.php?qv=150&tsv=1107&wNotes=on">RadioSensitizer</a>,
<!-- <a href="tbResList.php?qv=150&tsv=1185&wNotes=on">RadioProtective</a>, -->
<a href="tbResList.php?qv=150&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=150&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=150&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=150&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=150&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=150&tsv=1188&wNotes=on">CardioProtective</a>,

<br>
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=150&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
<br>


<table>
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
</tr>

<tr>
<td>1</td>
<td>PKM2-mediated aerobic glycolysis (Warburg metabolism)</td>
<td>↓</td>
<td>Energy / biomass restriction</td>
<td>Key, repeatedly reported mechanism: shikonin suppresses PKM2 activity and PKM2-driven glycolysis in multiple tumor models, with downstream growth inhibition and apoptosis</td>
</tr>

<tr>
<td>2</td>
<td>ROS accumulation / oxidative stress</td>
<td>↑ ROS</td>
<td>Redox overload</td>
<td>Common upstream trigger that drives mitochondrial dysfunction and regulated cell death programs; often precedes necroptosis/apoptosis signaling</td>
</tr>

<tr>
<td>3</td>
<td>Necroptosis core cascade (RIPK1 → RIPK3 → MLKL)</td>
<td>↑</td>
<td>Programmed necrotic cell death</td>
<td>Strong evidence across cancers (e.g., leukemia and nasopharyngeal carcinoma): shikonin increases RIPK1/RIPK3/MLKL expression/activation; necroptosis inhibitors can blunt the effect</td>
</tr>

<tr>
<td>4</td>
<td>Mitochondrial integrity (ΔΨm)</td>
<td>↓</td>
<td>Mitochondrial dysfunction</td>
<td>ROS-linked depolarization; acts as a pivot into intrinsic apoptosis and other death programs</td>
</tr>

<tr>
<td>5</td>
<td>Intrinsic apoptosis (BAX/BAK → Caspase-9/3)</td>
<td>↑</td>
<td>Programmed cell death</td>
<td>Frequently observed; often framed as ROS → mitochondrial damage → caspase-dependent apoptosis</td>
</tr>

<tr>
<td>6</td>
<td>PKM2/STAT3 signaling axis</td>
<td>↓</td>
<td>Reduced survival &amp; proliferation signaling</td>
<td>In ESCC and related models, shikonin suppresses PKM2-driven glycolysis and down-modulates STAT3 pathway activity</td>
</tr>

<tr>
<td>7</td>
<td>NF-κB pathway</td>
<td>↓</td>
<td>Reduced pro-survival transcription</td>
<td>Reported as part of multi-target suppression of inflammatory/anti-apoptotic programs in several tumor models and reviews</td>
</tr>

<tr>
<td>8</td>
<td>PI3K–AKT (± mTOR)</td>
<td>↓</td>
<td>Growth &amp; resistance pathway inhibition</td>
<td>Often described as sensitizing cells to apoptosis/TRAIL; may be secondary to oxidative stress and metabolic collapse</td>
</tr>

<tr>
<td>9</td>
<td>Stress MAPKs (JNK / p38)</td>
<td>↑</td>
<td>Pro-death stress signaling</td>
<td>Common downstream response to ROS; can reinforce apoptosis and other death outcomes</td>
</tr>

<tr>
<td>10</td>
<td>Ferroptosis-related axis (lipid peroxidation; GPX4)</td>
<td>↑ lipid perox / ↓ GPX4</td>
<td>Iron-dependent oxidative death</td>
<td>Reported prominently for acetylshikonin (a shikonin derivative): ROS-associated lipid peroxidation with reduced GPX4 expression alongside RIPK1/RIPK3/MLKL activation</td>
</tr>

<tr>
<td>11</td>
<td>Endoplasmic reticulum stress (UPR / ERS)</td>
<td>↑</td>
<td>Proteotoxic stress signaling</td>
<td>Frequently mentioned in leukemia-focused mechanism summaries and broader reviews as contributory to growth arrest and death</td>
</tr>

<tr>
<td>12</td>
<td>Multiple regulated death programs (apoptosis / necroptosis / ferroptosis / pyroptosis)</td>
<td>↑ (context-dependent)</td>
<td>Broader cell-death engagement</td>
<td>Recent reviews emphasize that shikonin can engage several programmed cell death modalities depending on cell context and dosing</td>
</tr>
</table>



<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>PKM2-mediated aerobic glycolysis (Warburg metabolism)</td>
<td>↓ PKM2 activity / ↓ glycolysis</td>
<td>Energy &amp; biomass restriction</td>
<td>Demonstrates shikonin (and analogs) inhibit cancer glycolysis, reducing glucose consumption/lactate production via PKM2 targeting</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21516121/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>PKM2 → STAT3 signaling axis</td>
<td>↓ PKM2-driven signaling / ↓ STAT3 pathway</td>
<td>Reduced survival &amp; proliferation</td>
<td>ESCC study: shikonin suppresses PKM2-mediated aerobic glycolysis and regulates PKM2/STAT3 signaling</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8247391/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>Necroptosis (RIPK1 → RIPK3 → MLKL)</td>
<td>↑ RIPK1/RIPK3/MLKL</td>
<td>Programmed necrotic cell death</td>
<td>Nasopharyngeal carcinoma: shikonin induces necroptosis with upregulation of RIPK1/RIPK3/MLKL (with ROS involvement)</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6498394/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>ROS accumulation</td>
<td>↑ ROS</td>
<td>Oxidative stress trigger</td>
<td>Colon cancer model: shikonin increases intracellular ROS; ROS functions upstream of apoptosis</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5752506/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>Mitochondrial apoptosis (Caspase-9/3)</td>
<td>↑ Caspase-9/3</td>
<td>Programmed cell death</td>
<td>Same colon cancer study shows shikonin increases caspase-3 and caspase-9 activity (mitochondria-mediated apoptosis)</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5752506/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>ER stress / UPR (PERK → eIF2α → CHOP)</td>
<td>↑</td>
<td>Proteotoxic stress apoptosis signaling</td>
<td>Colon cancer: shikonin-induced apoptosis mediated by PERK/eIF2α/CHOP ER-stress pathway</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6319547/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>Autophagic flux (autophagosome–lysosome completion)</td>
<td>↓ autophagic flux (blocked)</td>
<td>ROS + apoptosis amplification</td>
<td>Colorectal cancer: shikonin induces ROS and apoptosis by inhibiting autophagic flux</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6930377/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB activity</td>
<td>Reduced pro-survival transcription</td>
<td>Pancreatic cancer xenograft/mechanistic study: shikonin suppresses NF-κB activity and NF-κB–regulated gene products</td>
<td><a href="https://www.sciencedirect.com/science/article/pii/S000629521400080X" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>PI3K–AKT–mTOR (stemness / chemoresistance axis)</td>
<td>↓ PI3K/AKT/mTOR</td>
<td>Reduced survival &amp; stemness</td>
<td>Chemoresistant lung cancer CSC context: shikonin attenuates PI3K–Akt–mTOR pathway and reduces cancer stemness</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10779050/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>Cell cycle control (p21; G2/M arrest)</td>
<td>↑ p21 / ↑ G2/M arrest</td>
<td>Proliferation block</td>
<td>Gastric cancer (AGS): shikonin induces cell-cycle arrest linked to p21 regulation</td>
<td><a href="https://europepmc.org/article/med/24384380" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>Invasion / metastasis programs (NF-κB-linked)</td>
<td>↓ invasion</td>
<td>Anti-invasive phenotype</td>
<td>Reports shikonin inhibits tumor invasion via down-regulation of NF-κB–related mechanisms in a high-metastatic tumor model</td>
<td><a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1601-0825.2010.01758.x" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>Chemosensitization via glycolysis suppression</td>
<td>↓ glycolysis / ↑ cisplatin sensitivity</td>
<td>Combination benefit</td>
<td>NSCLC: shikonin inhibits glycolysis and sensitizes cells to cisplatin (explicitly connecting metabolic suppression to chemosensitization)</td>
<td><a href="https://www.tandfonline.com/doi/full/10.1080/21655979.2022.2086378" target="_blank">(ref)</a></td>
</tr>

</table>



Pathway results for Effect on Cancer / Diseased Cells

Redox & Oxidative Stress ⓘ

4-HNE↑, 1,   ATF3↑, 1,   Catalase↓, 2,   Fenton↑, 1,   Ferroptosis↑, 6,   Ferroptosis↓, 1,   GPx↑, 1,   GPx4↓, 8,   GSH↓, 11,   GSH↑, 1,   GSH/GSSG↓, 4,   H2O2↑, 2,   HK1↓, 1,   HO-1⇅, 1,   HO-1↑, 2,   Iron↑, 5,   Keap1↑, 2,   lipid-P↑, 5,   MDA↑, 3,   Nrf1↑, 1,   NRF2↓, 4,   OXPHOS⇅, 1,   PYCR1↓, 1,   ROS↓, 1,   ROS↑, 42,   ROS?, 1,   i-ROS↑, 1,   SOD↓, 1,   SOD1↑, 1,   TrxR↓, 1,   TrxR1↓, 3,   xCT↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 6,   MMP↓, 14,   mtDam↑, 1,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 1,   ECAR↓, 1,   FASN↓, 1,   G6PD↓, 1,   GlucoseCon↓, 11,   Glycolysis↓, 19,   ac‑Histones↑, 1,   HK2↓, 5,   lactateProd↓, 17,   LDH↓, 1,   LDH∅, 1,   LDH↝, 1,   LDHA∅, 1,   PDH∅, 1,   PDK1↓, 2,   PFK1↓, 1,   PFK2↓, 1,   PFKFB2↓, 1,   p‑PKM2↓, 1,   PKM2↓, 35,   PKM2∅, 1,   SIRT1↑, 1,   SIRT2↑, 1,   Warburg↓, 3,  

Cell Death ⓘ

p‑Akt↑, 1,   p‑Akt↓, 2,   Akt↓, 9,   Apoptosis↑, 22,   Apoptosis↓, 1,   Apoptosis?, 1,   ATF2↓, 1,   BAX↑, 4,   BAX↓, 1,   Bcl-2↓, 8,   Bcl-2↑, 2,   Bcl-xL↓, 1,   Casp↑, 4,   Casp3↑, 9,   proCasp3↓, 1,   proCasp3↑, 1,   cl‑Casp3↑, 2,   cl‑Casp3↓, 1,   Casp7↑, 1,   cl‑Casp8↑, 1,   Casp8↑, 1,   Casp9↑, 5,   Cyt‑c↑, 4,   DR5↑, 1,   Endon↑, 1,   Ferroptosis↑, 6,   Ferroptosis↓, 1,   GranB↑, 1,   GRP58↓, 1,   GSDME↑, 1,   JNK↑, 4,   p‑JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   Myc↓, 1,   Necroptosis↑, 8,   p38↑, 2,   p38↓, 1,   p‑p38↑, 1,   Perforin↑, 1,   Pyro↑, 1,   RIP1↑, 6,   RIP1↓, 2,   survivin↓, 1,   TRAIL↑, 1,   TumCD↑, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,  

Transcription & Epigenetics ⓘ

DLEU1↓, 1,   other↑, 1,   other↓, 1,   other↝, 1,   tumCV↓, 7,  

Protein Folding & ER Stress ⓘ

CHOP↑, 4,   eIF2α↓, 1,   eIF2α↑, 3,   p‑eIF2α↑, 2,   ER Stress↑, 3,   GRP78/BiP↑, 1,   HSP70/HSPA5↑, 1,   IRE1↑, 1,   PERK↑, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B↑, 1,   LC3B-II↑, 1,   LC3I↑, 1,   p62↑, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

DFF45↓, 1,   DNAdam↑, 4,   DNMT1↓, 2,   P53↑, 8,   cl‑PARP↑, 7,   PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 2,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 2,   P21↓, 1,   P21↑, 3,   TumCCA↑, 13,   TumCCA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

4E-BP1↓, 1,   CSCs↓, 1,   Diff↑, 2,   EMT↓, 3,   p‑ERK↑, 2,   p‑ERK↓, 2,   ERK↓, 4,   ERK↑, 1,   FLT3↓, 1,   FOXO3↑, 1,   GSK‐3β↑, 1,   GTPBP4↓, 1,   HDAC1↓, 1,   IGF-1↓, 1,   p‑IGF-1↓, 1,   mTOR↓, 7,   mTOR↑, 1,   Nanog↓, 1,   OCT4↓, 1,   P70S6K↓, 1,   PI3K↓, 9,   PTEN↑, 2,   Src↓, 2,   Src↑, 1,   p‑STAT3↓, 2,   TumCG↓, 12,  

Migration ⓘ

Ca+2↑, 3,   Ca+2↓, 1,   mt-Ca+2↑, 1,   CD11b↑, 1,   E-cadherin↑, 2,   FAK↓, 2,   ITGB1↓, 1,   Ki-67↓, 1,   miR-155↓, 1,   MMP13↓, 2,   MMP2↓, 2,   MMP3↓, 1,   MMP7↓, 2,   MMP9↓, 4,   MMPs↓, 1,   N-cadherin↓, 1,   PAK1↓, 1,   RIP3↑, 5,   RIP3↓, 1,   Snail↓, 1,   TGF-β↓, 2,   TIMP1↑, 1,   TumCA↓, 1,   TumCI↓, 12,   TumCMig↓, 13,   TumCP↓, 23,   TumMeta↓, 1,   uPA↓, 1,   VCAM-1↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↓, 1,   ATF4↑, 2,   EGFR↓, 5,   p‑EGFR↓, 1,   EGR1↑, 1,   Hif1a↓, 6,   Hif1a↑, 1,   KDR/FLK-1↓, 1,   TAMS↝, 1,   VEGF↓, 2,   VM↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 6,   GLUT1∅, 1,   GLUT3∅, 1,   GLUT3↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD14↑, 1,   COX2↓, 3,   Gal1↑, 1,   HMGB1↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL1β↓, 1,   IL6↓, 2,   JAK1?, 1,   p‑JAK1↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 10,   NK cell↑, 1,   p65↓, 1,   PD-L1↓, 1,   TLR2↓, 1,   TNF-α↓, 1,  

Cellular Microenvironment ⓘ

ADAM17↓, 1,   pH↝, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   ChemoSen↑, 8,   Dose↝, 2,   eff↝, 3,   eff↓, 14,   eff↑, 8,   eff⇅, 1,   Half-Life↝, 2,   Half-Life↓, 1,   MDR1↓, 1,   RadioS↑, 1,   selectivity↑, 11,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 5,   p‑EGFR↓, 1,   ERα/ESR1↓, 1,   Ferritin↓, 1,   GutMicro↑, 1,   IL6↓, 2,   Ki-67↓, 1,   LDH↓, 1,   LDH∅, 1,   LDH↝, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 2,   cardioP↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   OS↑, 3,   QoL↑, 1,   Remission↑, 1,   TumVol↓, 4,   TumW↓, 3,   Weight↑, 1,  
Total Targets: 277

Pathway results for Effect on Normal Cells

Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 1,   CYP1A1↑, 1,   Ferroptosis↓, 1,   GCLC↑, 1,   GPx↑, 1,   GPx4↓, 1,   GSH↑, 5,   GSS↑, 1,   HO-1↝, 1,   HO-1↑, 5,   Iron↓, 1,   lipid-P↑, 1,   MDA↓, 2,   MPO↓, 3,   NQO1↑, 2,   NRF2↑, 10,   NRF2↓, 1,   ROS↓, 9,   ROS?, 1,   ROS↑, 1,   SOD↑, 6,   TAC↑, 1,  

Metal & Cofactor Biology ⓘ

NCOA4↝, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 3,   AMPK↑, 1,   CYP2C6↑, 1,   CYP3A2↑, 1,   lactateProd↓, 1,   PKM2↓, 3,   SIRT1↑, 1,   SIRT1↓, 1,  

Cell Death ⓘ

AhR↑, 1,   Akt↑, 1,   p‑Akt↑, 1,   Apoptosis↓, 2,   BAX↓, 3,   Bcl-2↑, 3,   Casp1↓, 1,   Casp12↓, 1,   cl‑Casp3↓, 1,   Casp3↓, 1,   Casp3↑, 1,   Ferroptosis↓, 1,   iNOS↓, 2,   JNK↓, 1,   p‑p38↓, 1,   p38↓, 1,  

Transcription & Epigenetics ⓘ

p‑cJun↓, 1,   other↑, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   p‑eIF2α↓, 1,   ER Stress↓, 1,   GRP78/BiP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   p‑ERK↓, 1,   ERK↓, 1,   Mst1↓, 1,   PI3K↑, 1,   p‑PTEN↓, 1,   STAT3↑, 1,   TumCG↓, 1,  

Migration ⓘ

ARG↑, 1,   CYP2D1↑, 1,   E-sel↓, 1,   TGF-β↑, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   NO↓, 1,  

Barriers & Transport ⓘ

NHE3↑, 1,  

Immune & Inflammatory Signaling ⓘ

AIM2↓, 1,   COX2↓, 1,   HMGB1↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   p‑IKKα↓, 1,   IL10↑, 1,   IL10↓, 1,   IL17↓, 2,   IL18↓, 1,   IL1β↓, 4,   IL6↓, 5,   IL8↓, 1,   Inflam?, 1,   Inflam↓, 7,   NF-kB↓, 3,   NF-kB↑, 1,   p‑NF-kB↓, 1,   p‑p50↓, 1,   p‑p65↓, 1,   TNF-α↓, 7,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   CYP1A2↑, 1,   Dose↝, 1,   eff↑, 2,   eff↓, 3,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 3,   AST↓, 3,   BMD↑, 1,   IL6↓, 5,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 2,   hepatoP↑, 3,   motorD↑, 1,   neuroP↑, 5,   RenoP↑, 3,   toxicity↓, 3,   toxicity∅, 2,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 114

Research papers

Year Title Authors PMID Link Flag
2025Inhibition of PKM2 by shikonin impedes TGF-β1 expression by repressing histone lactylation to alleviate renal fibrosisTianya Xiang39700636https://pubmed.ncbi.nlm.nih.gov/39700636/0
2025Induction of Ferroptosis by Shikonin in Gastric Cancer via the DLEU1/mTOR/GPX4 AxisYiying Wang40126008https://pubmed.ncbi.nlm.nih.gov/40126008/0
2024Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axisRui HuangPMC11656048https://pmc.ncbi.nlm.nih.gov/articles/PMC11656048/0
2024Shikonin Induces Autophagy and Apoptosis in Esophageal Cancer EC9706 Cells by Regulating the AMPK/mTOR/ULK AxisJunli ZhangPMC11537739https://pmc.ncbi.nlm.nih.gov/articles/PMC11537739/0
2024Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matterKristina Shilnikova—https://onlinelibrary.wiley.com/doi/full/10.1002/cbin.122330
2024Shikonin Suppresses Cell Tumorigenesis in Gastric Cancer Associated with the Inhibition of c-Myc and Yap-1Fei Zhang37957853https://pubmed.ncbi.nlm.nih.gov/37957853/0
2024ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironmentJuan ZhangPMC11077861https://pmc.ncbi.nlm.nih.gov/articles/PMC11077861/0
2024SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2Bolin LianPMC11384727https://pmc.ncbi.nlm.nih.gov/articles/PMC11384727/0
2024Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 PathwayQian HuangPMC11844683https://pmc.ncbi.nlm.nih.gov/articles/PMC11844683/0
2024Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axisCongcong Lu—https://www.sciencedirect.com/science/article/abs/pii/S09447113240079670
2024Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen speciesKe Qi—https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1416781/full0
2024Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in miceHu TuoPMC10776756https://pmc.ncbi.nlm.nih.gov/articles/PMC10776756/0
2024Simple ROS-responsive micelles loaded Shikonin for efficient ovarian cancer targeting therapy by disrupting intracellular redox homeostasisKangyuan Hu39370057https://pubmed.ncbi.nlm.nih.gov/39370057/0
2024Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysisChen YangPMC11734080https://pmc.ncbi.nlm.nih.gov/articles/PMC11734080/0
2024Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 InhibitorYen-Hsiang HuangPMC10779050https://pmc.ncbi.nlm.nih.gov/articles/PMC10779050/0
2024Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2Shaoyi Cao—https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-02187-70
2024Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulationJinghua ChenPMC10771352https://pmc.ncbi.nlm.nih.gov/articles/PMC10771352/0
2024Shikonin attenuates cerebral ischemia/reperfusion injury via inhibiting NOD2/RIP2/NF-κB-mediated microglia polarization and neuroinflammation—https://www.strokejournal.org/article/S1052-3057(24)00134-4/abstract0
2023Promising Nanomedicines of Shikonin for Cancer TherapyYan C—https://www.dovepress.com/promising-nanomedicines-of-shikonin-for-cancer-therapy-peer-reviewed-fulltext-article-IJN0
2023Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in miceZhiwei Weng39491143https://pubmed.ncbi.nlm.nih.gov/39491143/0
2023Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulationXinyu Qian37268198https://pubmed.ncbi.nlm.nih.gov/37268198/0
2023Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt CascadesMohamed F BalahaPMC10215741https://pmc.ncbi.nlm.nih.gov/articles/PMC10215741/0
2023Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A reviewShuangxia ZhangPMC10589597https://pmc.ncbi.nlm.nih.gov/articles/PMC10589597/0
2023Systemic administration of Shikonin ameliorates cognitive impairment and neuron damage in NPSLE miceJiali Ni—https://www.sciencedirect.com/science/article/pii/S01655728230015220
2023Shikonin Exerts an Antileukemia Effect against FLT3-ITD Mutated Acute Myeloid Leukemia Cells via Targeting FLT3 and Its Downstream Pathways—https://karger.com/aha/article-abstract/147/3/310/869454/Shikonin-Exerts-an-Antileukemia-Effect-against?redirectedFrom=fulltext0
2023Shikonin inhibits immune checkpoint PD-L1 expression on macrophage in sepsis by modulating PKM2Lijia Yuan37302371https://pubmed.ncbi.nlm.nih.gov/37302371/0
2023Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted deliveryLi LongPMC10170793https://pmc.ncbi.nlm.nih.gov/articles/PMC10170793/0
2023Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancerXiaojie Liu37421765https://pubmed.ncbi.nlm.nih.gov/37421765/0
2023PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolismHongyan Lin—https://www.sciencedirect.com/science/article/abs/pii/S02235234230008180
2023Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injuryWenjia Xie—https://www.nature.com/articles/s41419-023-06195-z0
2022Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cellsJunli ZhangPMC9208523https://pmc.ncbi.nlm.nih.gov/articles/PMC9208523/0
2022Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathwayYitian DaiPMC9275963https://pmc.ncbi.nlm.nih.gov/articles/PMC9275963/0
2022GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolismQiang ZhouPMC9483790https://pmc.ncbi.nlm.nih.gov/articles/PMC9483790/0
2022Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling PathwayHongjie DuPMC8908960https://pmc.ncbi.nlm.nih.gov/articles/PMC8908960/0
2022Natural shikonin and acetyl-shikonin improve intestinal microbial and protein composition to alleviate colitis-associated colorectal cancerHongyan Lin35952517https://pubmed.ncbi.nlm.nih.gov/35952517/0
2022Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer CellsHui QiPMC8692675https://pmc.ncbi.nlm.nih.gov/articles/PMC8692675/0
2022Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer CellsWenjing JiPMC9102431https://pmc.ncbi.nlm.nih.gov/articles/PMC9102431/0
2022Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagyWenxia LiPMC9641271https://pmc.ncbi.nlm.nih.gov/articles/PMC9641271/0
2022Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis AmplificationWenjie Feng35944147https://pubmed.ncbi.nlm.nih.gov/35944147/0
2021Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte ProliferationYun-zi LiuPMC8558409https://pmc.ncbi.nlm.nih.gov/articles/PMC8558409/0
2021Shikonin Inhibits Non-Small-Cell Lung Cancer H1299 Cell Growth through Survivin Signaling PathwayHaini WanPMC8590588https://pmc.ncbi.nlm.nih.gov/articles/PMC8590588/0
2021Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancerLiying Sha—https://www.spandidos-publications.com/10.3892/mmr.2021.121990
2021Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathwaysJiahui LiPMC8440543https://pmc.ncbi.nlm.nih.gov/articles/PMC8440543/0
2021Shikonin Alleviates Endothelial Cell Injury Induced by ox-LDL via AMPK/Nrf2/HO-1 Signaling PathwayShuang LiuPMC8668324https://pmc.ncbi.nlm.nih.gov/articles/PMC8668324/0
2021Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF SignalingYanqiu Jia—https://onlinelibrary.wiley.com/doi/full/10.1155/2021/55642460
2021Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL-6/STAT3 signaling pathwayWei ShiPMC8577797https://pmc.ncbi.nlm.nih.gov/articles/PMC8577797/0
2021Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell lineWei Yang33220292https://pubmed.ncbi.nlm.nih.gov/33220292/0
2021Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activationMatin AlaviPMC8557610https://pmc.ncbi.nlm.nih.gov/articles/PMC8557610/0
2021Shikonin Inhibits Tumor Growth of ESCC by suppressing PKM2 mediated Aerobic Glycolysis and STAT3 PhosphorylationQiqi ZhangPMC8247391https://pmc.ncbi.nlm.nih.gov/articles/PMC8247391/0
2021Molecular mechanism of shikonin inhibiting tumor growth and potential application in cancer treatmentQiang WangPMC8692723https://pmc.ncbi.nlm.nih.gov/articles/PMC8692723/0
2020Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathwaysKai Chen32272431https://pubmed.ncbi.nlm.nih.gov/32272431/0
2020Regulation of glycolysis and the Warburg effect in wound healingRoohi Vinaik—https://insight.jci.org/articles/view/1389490
2020Shikonin induces cell death by inhibiting glycolysis in human testicular cancer I-10 and seminoma TCAM-2 cellsNan FangPMC7544591https://pmc.ncbi.nlm.nih.gov/articles/PMC7544591/0
2020Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axisNan ZhangPMC6930377https://pmc.ncbi.nlm.nih.gov/articles/PMC6930377/0
2020Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathwayJingjing Zhang32282369https://pubmed.ncbi.nlm.nih.gov/32282369/0
2019Pharmacological properties and derivatives of shikonin-A review in recent yearsChuanjie Guo31553936https://pubmed.ncbi.nlm.nih.gov/31553936/0
2019Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathwaysYongkang Liu30873870https://pubmed.ncbi.nlm.nih.gov/30873870/0
2019Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signalingYan Chen—https://www.sciencedirect.com/science/article/abs/pii/S00062952193016500
2019Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expressionTiancong LiuPMC6498394https://pmc.ncbi.nlm.nih.gov/articles/PMC6498394/0
2019Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathwayBing Liu30475643https://pubmed.ncbi.nlm.nih.gov/30475643/0
2019The role of pyruvate kinase M2 in anticancer therapeutic treatmentsQiongli SuPMC6865080https://pmc.ncbi.nlm.nih.gov/articles/PMC6865080/0
2019Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)Andrew D. James—https://www.nature.com/articles/s41416-019-0675-30
2019Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin Through Regulating PKM2Tong Liu—https://www.dovepress.com/experimental-study-of-hepatocellular-carcinoma-treatment-by-shikonin-t-peer-reviewed-fulltext-article-JHC0
2019Shikonin derivatives for cancer prevention and therapyJoelle C. Boulos—https://www.sciencedirect.com/science/article/abs/pii/S03043835193027080
2018RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxideBin Lu29608987https://pubmed.ncbi.nlm.nih.gov/29608987/0
2018Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β SignalingHuachao LiPMC6337349https://pmc.ncbi.nlm.nih.gov/articles/PMC6337349/0
2018Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1Yue ZhangPMC5804303https://pmc.ncbi.nlm.nih.gov/articles/PMC5804303/0
2018Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic GlycolysisXiaoyue ZhaoPMC6162216https://pmc.ncbi.nlm.nih.gov/articles/PMC6162216/0
2018PKM2 Inhibitor Shikonin Overcomes the Cisplatin Resistance in Bladder Cancer by Inducing NecroptosisYonggang WangPMC6231221https://pmc.ncbi.nlm.nih.gov/articles/PMC6231221/0
2018Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated PathwaysXia HanPMC6319547https://pmc.ncbi.nlm.nih.gov/articles/PMC6319547/0
2018Shikonin upregulates the expression of drug-metabolizing enzymes and drug transporters in primary rat hepatocytesChin-Shiu Huang29414119https://pubmed.ncbi.nlm.nih.gov/29414119/0
2018Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivoJian-Cai TangPMC5743709https://pmc.ncbi.nlm.nih.gov/articles/PMC5743709/0
2018Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cellsJing ChenPMC5920510https://pmc.ncbi.nlm.nih.gov/articles/PMC5920510/0
2018Shikonin Suppresses Lymphangiogenesis via NF-κB/HIF-1α Axis InhibitionOrawin Prangsaengtong30381665https://pubmed.ncbi.nlm.nih.gov/30381665/0
2017Enhancement of NK cells proliferation and function by ShikoninYan Li28303727https://pubmed.ncbi.nlm.nih.gov/28303727/0
2017RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen speciesZijian Zhou28108311https://pubmed.ncbi.nlm.nih.gov/28108311/0
2017The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathwaysYe Tian—https://pubs.rsc.org/en/content/articlepdf/2017/ra/c7ra03291a0
2017Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signalingMing Yue Li28684144https://pubmed.ncbi.nlm.nih.gov/28684144/0
2017Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathwayXia Li27864022https://pubmed.ncbi.nlm.nih.gov/27864022/0
2017Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancerWenquan LiangPMC5752506https://pmc.ncbi.nlm.nih.gov/articles/PMC5752506/0
2016PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cellsWenjuan LiPMC4827433https://pmc.ncbi.nlm.nih.gov/articles/PMC4827433/0
2016Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen speciesWenquan LiangPMC5131274https://pmc.ncbi.nlm.nih.gov/articles/PMC5131274/0
2016Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathwaysHUILING JINGPMC4805065https://pmc.ncbi.nlm.nih.gov/articles/PMC4805065/0
2016Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivoGuodong He26740178https://pubmed.ncbi.nlm.nih.gov/26740178/0
2016Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma CellsHyeonseok KoPMC5012875https://pmc.ncbi.nlm.nih.gov/articles/PMC5012875/0
2016PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activationMin XiePMC5093342https://pmc.ncbi.nlm.nih.gov/articles/PMC5093342/0
2015Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathwayJi Ping Liu25880237https://pubmed.ncbi.nlm.nih.gov/25880237/0
2015Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell ProliferationWenjuan LiPMC4427333https://pmc.ncbi.nlm.nih.gov/articles/PMC4427333/0
2015Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 ExpressionYueh-Chiao YehPMC4337265https://pmc.ncbi.nlm.nih.gov/articles/PMC4337265/0
2014Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathwayYongwei Wang—https://www.sciencedirect.com/science/article/abs/pii/S000629521400080X0
2014An Oxidative Stress Mechanism of Shikonin in Human Glioma CellsJen-Tsung YangPMC3979747https://pmc.ncbi.nlm.nih.gov/articles/PMC3979747/0
2013Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathwayHeyong Wang—https://www.sciencedirect.com/science/article/abs/pii/S0300483X130007720
2013Shikonin induces cell cycle arrest in human gastric cancer (AGS) by early growth response 1 (Egr1)-mediated p21 gene expression.Kim SJ—https://europepmc.org/article/med/243843800
2013Pharmacological Properties of Shikonin – A Review of Literature since 2002Isabel Andújar—https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0033-1350934.pdf0
2013The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosisZeze FuPMC4028842https://pmc.ncbi.nlm.nih.gov/articles/PMC4028842/0
2012Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer CellsBenjamin WienchPMC3478753https://pmc.ncbi.nlm.nih.gov/articles/PMC3478753/0
2012The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE PathwayBo ZhangPMC3478756https://pmc.ncbi.nlm.nih.gov/articles/PMC3478756/0
2012Novel multiple apoptotic mechanism of shikonin in human glioma cellsChing-Hsein Chen2446899https://pubmed.ncbi.nlm.nih.gov/22446899/0
2011Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinomaKe Gong—https://www.sciencedirect.com/science/article/abs/pii/S08915849110058430
2011Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cellsR Min21029262https://pubmed.ncbi.nlm.nih.gov/21029262/0
2011Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2J Chen21516121https://pubmed.ncbi.nlm.nih.gov/21516121/0
2010Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cellsI-Chang Chang20460760https://pubmed.ncbi.nlm.nih.gov/20460760/0
2010A novel antiestrogen agent Shikonin inhibits estrogen-dependent gene transcription in human breast cancer cellsYuan Yao19760501https://pubmed.ncbi.nlm.nih.gov/19760501/0
2004Shikonin Induces Apoptosis by Inhibiting Phosphorylation of IGF-1 Receptor in Myeloma Cells.Takehiro Kimura, MD—https://ashpublications.org/blood/article/104/11/4858/55900/Shikonin-Induces-Apoptosis-by-Inhibiting0
1991Clinical trial on the effects of shikonin mixture on later stage lung cancerX P Guo1806305https://pubmed.ncbi.nlm.nih.gov/1806305/0