tbResList Print — BetA Betulinic acid

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Product

BetA Betulinic acid
Description: <b>Betulinic acid</b> "buh-TOO-li-nik acid" is a natural compound with antiretroviral, anti malarial, anti-inflammatory and anticancer properties. It is found in the bark of several plants, such as white birch, ber tree and rosemary, and has a complex mode of action against tumor cells.<br>
-Betulinic acid is a naturally occurring pentacyclic triterpenoid<br>
-vitro concentrations range from 1–100 µM, in vivo studies in rodents have generally used doses from 10–100 mg/kg<br>
Precursor: Betulin, via oxidation at C-28<br>
Lipophilicity: High (poor aqueous solubility)<br>

-<a href="tbResList.php?qv=42&tsv=1109&wNotes=on&exSp=open">half-life</a> reports vary 3-5 hrs?.
Reported half-life varies by formulation and species; several studies report multi-hour systemic persistence.<br>
<a href="tbResList.php?qv=42&tsv=792&wNotes=on&exSp=open">BioAv</a> -hydrophobic molecule with relatively poor water solubility. <br>

<pre>
Main Cancer action
-Direct mitochondrial targeting in cancer cells
-Minimal effect on normal cells

Key pathways
-Mitochondrial membrane permeabilization
-ROS-mediated apoptosis
-Caspase-independent death

Chemo relevance: Generally compatible, Not a redox buffer
</pre>
<br>
Pathways:<br>

<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- often induce
<a href="tbResList.php?qv=42&tsv=275&wNotes=on">ROS</a> production<br>
- ROS↑ related:
<a href="tbResList.php?&qv=42&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?&qv=42&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?&qv=42&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?&qv=42&tsv=356&wNotes=on">GRP78↑</a>,
<a href="tbResList.php?&qv=42&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?&qv=42&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?&qv=42&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?&qv=42&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?&qv=42&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?&qv=42&wNotes=on&word=HSP">HSP↓</a>
<br>

<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Lowers AntiOxidant defense in Cancer Cells(Often associated with reduced redox buffering capacity in tumor cells (e.g., GSH depletion); NRF2 direction model-dependent.):
<a href="tbResList.php?&qv=42&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?&qv=42&tsv=298&wNotes=on&word=SOD↓">SOD↓</a>,
<a href="tbResList.php?&qv=42&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<br>

- May Raise
<a href="tbResList.php?&qv=42&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?&qv=42&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?&qv=42&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?&qv=42&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?&qv=42&tsv=46&wNotes=on&word=Catalase↑">Catalase↑</a>
Reports suggest relative sparing of normal cells and preservation of antioxidant capacity in some models
<br>

<!-- INFLAMMATION : NF-kB↓, COX2↓, COX2↓ PRO-INFL CYTOKINES: IL-1β↓, TNF-α↓, IL-6↓, IL-8↓, -->
- lowers
<a href="tbResList.php?&qv=42&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?&qv=42&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>(typ),
<a href="tbResList.php?&qv=42&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?&qv=42&tsv=235&wNotes=on&word=p38↓">p38↓</a>
(context-dependent; often stress-activated), Pro-Inflammatory Cytokines :
<a href="tbResList.php?&qv=42&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?&qv=42&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?&qv=42&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?&qv=42&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=42&tsv=96&wNotes=on"EMT↓</a>,
<a href="tbResList.php?&qv=42&tsv=204&wNotes=on">MMPs↓</a>,
<a href="tbResList.php?&qv=42&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?&qv=42&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?&qv=42&tsv=308&wNotes=on">TIMP2</a>,
<a href="tbResList.php?&qv=42&tsv=415&wNotes=on">IGF-1↓</a>,
<a href="tbResList.php?&qv=42&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=42&tsv=1284&wNotes=on">ROCK1↓</a>,
<a href="tbResList.php?&qv=42&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=42&tsv=214&wNotes=on">NF-κB↓</a>,
<a href="tbResList.php?&qv=42&tsv=304&wNotes=on">TGF-β↓</a>,
<a href="tbResList.php?&qv=42&tsv=719&wNotes=on">α-SMA↓</a>,
<a href="tbResList.php?&qv=42&tsv=105&wNotes=on">ERK↓</a>
<br>

<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=42&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?&qv=42&wNotes=on&word=HSP">HSP↓</a>(model-dependent),
<a href="tbResList.php?&qv=42&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=42&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?&qv=42&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?&qv=42&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?&qv=42&tsv=894&wNotes=on">CDK4↓</a>,

<br>

<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?&qv=42&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?&qv=42&tsv=324&wNotes=on">TumCI↓</a>,
<a href="tbResList.php?&qv=42&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=42&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?&qv=42&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?&qv=42&tsv=1117&wNotes=on">TOP1↓</a>,
<br>

<!-- GLYCOLYSIS : ATP↓, HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓, lactateProd, OXPHOS -->
- inhibits
<a href="tbResList.php?qv=42&tsv=129&wNotes=on">glycolysis</a>
(secondary to mitochondrial stress)
<a href="tbResList.php?qv=42&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?&qv=42&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=42&tsv=772&wNotes=on">PKM2↓</a>,
<a href="tbResList.php?&qv=42&tsv=35&wNotes=on">cMyc↓</a>,
<a href="tbResList.php?&qv=42&tsv=566&wNotes=on&word=GLUT">GLUT1↓</a>,
<a href="tbResList.php?&qv=42&tsv=906&wNotes=on">LDH↓</a>,
<a href="tbResList.php?&qv=42&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<a href="tbResList.php?&qv=42&tsv=773&wNotes=on">HK2↓</a>,
<a href="tbResList.php?&qv=42&wNotes=on&word=PFK">PFKs↓</a>,
<a href="tbResList.php?&qv=42&wNotes=on&word=PDK">PDKs↓</a>,
<a href="tbResList.php?&qv=42&tsv=773&wNotes=on">HK2↓</a>,
<a href="tbResList.php?&qv=42&tsv=847&wNotes=on">ECAR↓</a>,
<a href="tbResList.php?&qv=42&tsv=356&wNotes=on">GRP78↑</a>(ER stress),
<a href="tbResList.php?&qv=42&tsv=623&wNotes=on">GlucoseCon↓</a>
<br>


<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=42&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=42&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=42&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=42&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<br>

<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- inhibits Cancer Stem Cells in some studies :
<a href="tbResList.php?qv=42&tsv=795&wNotes=on">CSC↓</a>,
<a href="tbResList.php?qv=42&tsv=124&wNotes=on">GLi1↓</a>,
<a href="tbResList.php?qv=42&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=42&tsv=508&wNotes=on">OCT4↓</a>,
<br>

<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=42&tsv=252&wNotes=on">PI3K↓</a>(typ),
<a href="tbResList.php?qv=42&tsv=4&wNotes=on">AKT↓</a>(typ),
<a href="tbResList.php?qv=42&wNotes=on&word=JAK">JAK↓</a>,
<a href="tbResList.php?qv=42&wNotes=on&word=STAT">STAT↓</a>,
<a href="tbResList.php?qv=42&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=42&tsv=9&wNotes=on">AMPK↓</a>(AMPK is often activated during metabolic stress),
<a href="tbResList.php?qv=42&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=42&tsv=168&wNotes=on">JNK</a>,
<br>



<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=42&tsv=1106&wNotes=on">chemo-sensitization</a>,
<a href="tbResList.php?qv=42&tsv=1171&wNotes=on">chemoProtective</a>,
<a href="tbResList.php?qv=42&tsv=1107&wNotes=on">RadioSensitizer</a>,
<a href="tbResList.php?qv=42&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=42&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=42&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=42&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=42&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=42&tsv=1188&wNotes=on">CardioProtective</a>,
<br>

<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=42&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
<br>
<br>



<!-- Betulinic Acid — Time-Scale Flagged Pathway Table (web-ready) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>

<tr>
<td>1</td>
<td>Intrinsic apoptosis (mitochondrial-mediated)</td>
<td>↑ mitochondria depolarization; ↑ cytochrome-c; ↑ caspase-9/3 activation</td>
<td>↔ limited activation (higher exposure required)</td>
<td>R, G</td>
<td>Execution of apoptosis</td>
<td>Betulinic acid (BA) is well known to engage the intrinsic apoptotic cascade, typically downstream of redox and signaling perturbations.</td>
</tr>

<tr>
<td>2</td>
<td>ROS / redox stress</td>
<td>↑ ROS (P→R)</td>
<td>↔ basal or antioxidant adaptation in some contexts</td>
<td>P, R</td>
<td>Stress induction</td>
<td>Many studies report ROS elevation in tumor cells exposed to BA; the direction and magnitude vary by cell type and exposure.</td>
</tr>

<tr>
<td>3</td>
<td>Mitochondrial permeability transition / ΔΨm loss</td>
<td>ΔΨm ↓ (R→G)</td>
<td>↔ maintained</td>
<td>R, G</td>
<td>Mitochondrial failure</td>
<td>Often observed as an early event preceding caspase activation in apoptosis studies.</td>
</tr>

<tr>
<td>4</td>
<td>PI3K / AKT / mTOR survival axis</td>
<td>↓ PI3K/AKT signaling; ↓ phospho-mTOR</td>
<td>↔</td>
<td>R, G</td>
<td>Survival/growth suppression</td>
<td>Betulinic acid often downregulates pro-survival kinase signaling, sensitizing cells to apoptosis and cytostasis.</td>
</tr>

<tr>
<td>5</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB activity</td>
<td>↔</td>
<td>R, G</td>
<td>Pro-survival/inflammatory transcription suppression</td>
<td>Reduction in NF-κB activity limits pro-survival gene expression; supports sensitization to stressors.</td>
</tr>

<tr>
<td>6</td>
<td>MAPK re-wiring (JNK / ERK / p38)</td>
<td>Stress-MAPK shifts; JNK/p38 often ↑; ERK context-dependent</td>
<td>↔</td>
<td>P, R</td>
<td>Early stress signaling</td>
<td>MAPK responses vary by model, with stress-associated p38/JNK often activated and ERK modulation variable.</td>
</tr>

<tr>
<td>7</td>
<td>Cell-cycle checkpoints (p21, p27, cyclins)</td>
<td>↑ p21/p27; ↑ G1/S or G2/M arrest</td>
<td>↔</td>
<td>G</td>
<td>Proliferation arrest</td>
<td>BA often induces cell-cycle blockade, slowing proliferation before apoptosis commitment.</td>
</tr>

<tr>
<td>8</td>
<td>Angiogenic signaling (VEGF & related)</td>
<td>↓ VEGF; anti-angiogenic outputs</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Typically seen at the level of reduced pro-angiogenic factor expression or secretion in longer-term assays.</td>
</tr>

<tr>
<td>9</td>
<td>EMT / invasion / migration programs (MMPs)</td>
<td>↓ MMP2/MMP9; ↓ migration/invasion</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Often measured as reduced invasive capacity and decreased expression of EMT markers in later time points.</td>
</tr>

<tr>
<td>10</td>
<td>Autophagy modulation</td>
<td>↑ LC3-II; ↑ autophagic flux (model dependent)</td>
<td>↔</td>
<td>G</td>
<td>Adaptive clearance / cell fate shift</td>
<td>BA can modulate autophagy, which may either sensitize cells to death pathways or reflect adaptive stress responses.</td>
</tr>

</table>

<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (primary/physical-chemical effects; rapid kinase/redox signaling)</li>
<li><b>R</b>: 30 min–3 hr (acute redox and stress-response activation)</li>
<li><b>G</b>: &gt;3 hr (gene-regulatory adaptation and phenotypic outcomes)</li>
</ul>









Pathway results for Effect on Cancer / Diseased Cells

Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ATF3↓, 1,   Ferroptosis↑, 2,   GCLM↓, 1,   GPx4↓, 1,   GSH↓, 1,   GSTA1↓, 1,   GSTs↓, 1,   HO-1↓, 1,   HO-1↑, 1,   Keap1↝, 1,   lipid-P↑, 1,   MDA↑, 1,   MDA↓, 1,   NRF2↓, 1,   NRF2↑, 1,   OXPHOS↓, 1,   ROS↑, 21,   ROS∅, 1,   ROS↓, 2,   i-ROS↑, 1,   mt-ROS↑, 3,   SOD↓, 1,   SOD2↓, 2,  

Metal & Cofactor Biology ⓘ

Ferritin↑, 1,   FTH1↓, 2,   NCOA4↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   ATP↓, 1,   CDC25↓, 1,   Insulin↓, 1,   MMP↓, 17,   mtDam↑, 1,   OCR↓, 3,  

Core Metabolism/Glycolysis ⓘ

ACSL1↓, 1,   AMPK↑, 2,   p‑AMPK↑, 1,   Cav1↑, 1,   cMyc↓, 2,   CPT1A↓, 1,   ECAR↓, 2,   FAO↓, 1,   FASN↓, 1,   GlucoseCon↓, 3,   Glycolysis↓, 4,   HK2↓, 1,   lactateProd↓, 3,   LDHA↓, 2,   p‑PDK1↓, 2,   PDK1↓, 3,   PFK1↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

p‑Akt↓, 3,   Apoptosis↑, 11,   Apoptosis↓, 1,   m-Apoptosis↑, 1,   mt-Apoptosis↑, 4,   BAD↑, 1,   BAX↑, 8,   Bax:Bcl2↑, 1,   Bcl-2↓, 9,   Bcl-2↑, 1,   Bcl-xL↓, 1,   Casp↑, 5,   Casp3↑, 7,   cl‑Casp3↑, 3,   Casp7↑, 2,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 7,   Cyt‑c↑, 12,   Diablo↑, 2,   Ferroptosis↑, 2,   JNK↓, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↓, 1,   p27↑, 1,   p38↑, 2,   survivin↓, 4,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 11,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   tumCV↓, 8,  

Protein Folding & ER Stress ⓘ

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

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   LC3B-II↑, 1,   LC3II↑, 1,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   DNAdam↑, 4,   P53↑, 1,   PARP↓, 1,   PARP↑, 1,   cl‑PARP↑, 2,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   Cyc↓, 1,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 2,   cycD1/CCND1↑, 1,   P21↑, 2,   TumCCA↑, 10,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   CSCs↓, 1,   EMT↓, 5,   ERK↓, 1,   Gli1↓, 1,   HDAC↓, 1,   IGF-1↓, 1,   mTOR↓, 2,   OCT4↓, 1,   P90RSK↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   PTCH1↓, 1,   RAS↓, 1,   STAT3↓, 5,   STAT3↑, 1,   p‑STAT3↓, 1,   TOP1↓, 11,   TumCG↓, 4,  

Migration ⓘ

Ca+2↑, 3,   E-cadherin↑, 2,   ER-α36↓, 1,   FAK↓, 1,   GLI2↓, 1,   Ki-67↓, 1,   LAMs↓, 1,   MALAT1↓, 1,   MMP2↓, 5,   MMP9↓, 5,   MMPs↓, 2,   N-cadherin↓, 2,   ROCK1↓, 1,   Slug↓, 1,   Smad1↑, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TIMP2↑, 2,   TumCI↓, 6,   TumCMig↓, 7,   TumCP↓, 5,   TumMeta↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   EGFR↓, 2,   Hif1a↓, 4,   VEGF↓, 11,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 2,   GLUT1↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   ICAM-1↓, 1,   IKKα↑, 1,   Inflam↓, 1,   JAK1↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 15,   NF-kB↑, 4,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 5,   ChemoSen↑, 11,   Dose↝, 2,   eff↓, 6,   eff↑, 5,   Half-Life↝, 1,   RadioS↑, 5,   selectivity↑, 8,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   Ferritin↑, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 2,   chemoP↑, 1,   chemoPv↑, 2,   neuroP↑, 1,   TumVol↓, 3,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 196

Pathway results for Effect on Normal Cells

Redox & Oxidative Stress ⓘ

antiOx↑, 3,   antiOx?, 1,   Catalase↑, 4,   GPx↑, 1,   GSH↑, 5,   GSR↑, 1,   HO-1↑, 2,   MDA↓, 4,   NOX4↓, 1,   NRF2↑, 3,   ROS↓, 8,   SOD?, 1,   SOD↑, 4,  

Mitochondria & Bioenergetics ⓘ

UCP1↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   GlucoseCon↑, 1,   Glycolysis↑, 2,   LDH↓, 2,  

Cell Death ⓘ

Apoptosis↓, 2,   p‑JNK↓, 1,   MAPK↓, 2,   p‑p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,  

Migration ⓘ

E-sel↓, 1,   heparanase↑, 1,   VCAM-1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 1,   IL10↑, 2,   IL12↓, 1,   IL17↓, 1,   IL1β↓, 2,   IL2↓, 1,   IL6↑, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 5,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 1,   TNF-α↑, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   IL6↑, 1,   IL6↓, 1,   LDH↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 2,   hepatoP↑, 2,   motorD↑, 1,   neuroP↑, 2,   RenoP↑, 2,   toxicity↓, 3,  
Total Targets: 61

Research papers

Year Title Authors PMID Link Flag
2025Betulinic Acid Inhibits Glioma Progression by Inducing Ferroptosis Through the PI3K/Akt and NRF2/HO-1 PathwaysJinxiang Huang—https://onlinelibrary.wiley.com/doi/10.1002/jgm.700110
2025Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generationDian Yuliartha Lestari—https://www.springermedicine.com/breast-cancer/breast-cancer/betulinic-acid-and-oleanolic-acid-modulate-cd81-expression-and-i/503020540
2024Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical StudiesElifsu Nemli—https://onlinelibrary.wiley.com/doi/10.1002/fsn3.46390
2024Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and PerspectivesSílvia FernandesPMC10889789https://pmc.ncbi.nlm.nih.gov/articles/PMC10889789/0
2024Unveiling Betulinic Acid as a Potent CDK4 Inhibitor for Cancer TherapeuticsBasiouny El-Gamal—https://ijper.org/article/doi/6036/0
2024Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivoPing Chen38403724https://link.springer.com/article/10.1007/s11418-024-01782-60
2024Cytotoxic Potential of Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Breast, Colon, and Lung Cancer Cell LinesAndreea MilanPMC11279467https://pmc.ncbi.nlm.nih.gov/articles/PMC11279467/0
2024Betulinic acid inhibits proliferation and triggers apoptosis in human breast cancer cells by modulating ER (α/β) and p53Yanvit Prompoon—https://www.scienceasia.org/2024.50.n5/scias50_2024085.pdf0
2024Cellular and molecular mechanisms underlying the potential of betulinic acid in cancer prevention and treatmentSubhasis Banerjee—https://www.sciencedirect.com/science/article/abs/pii/S09447113240051660
2024Role of natural secondary metabolites as HIF-1 inhibitors in cancer therapyPrem Shankar Mishra—https://link.springer.com/article/10.1007/s00044-024-03219-x0
2023Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradationLi Tao—https://www.sciencedirect.com/science/article/abs/pii/S03788741230016300
2023Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-β1 Signaling Pathway and Macrophage PolarizationJen-Lung ChenPMC9964887https://pmc.ncbi.nlm.nih.gov/articles/PMC9964887/0
2023Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathwayZhiru Xiu—https://www.sciencedirect.com/science/article/pii/S17564646230004150
2023Betulinic acid in the treatment of breast cancer: Application and mechanism progressHuijuan Mu—https://www.sciencedirect.com/science/article/abs/pii/S0367326X230019220
2022In silico profiling of histone deacetylase inhibitory activity of compounds isolated from Cajanus cajanKayode Ezekiel Adewole—https://www.researchgate.net/publication/357721542_In_silico_profiling_of_histone_deacetylase_inhibitory_activity_of_compounds_isolated_from_Cajanus_cajan0
2022Targeting Effect of Betulinic Acid Liposome Modified by Hyaluronic Acid on Hepatoma Cells In VitroXiaomei Wu—https://www.sciencedirect.com/science/article/abs/pii/S00223549220025810
2022Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegansHaiyan ChenPMC9372536https://pmc.ncbi.nlm.nih.gov/articles/PMC9372536/0
2022Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and MetastasisAmmad Ahmad FarooqiPMC9822120https://pmc.ncbi.nlm.nih.gov/articles/PMC9822120/0
2022Anti-Inflammatory Activities of Betulinic Acid: A ReviewJosé Fernando Oliveira-Costa—https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.883857/full0
2021Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal CancerLaphatrada YurasakpongPMC8588033https://pmc.ncbi.nlm.nih.gov/articles/PMC8588033/0
2021Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cellsYan ZhangPMC8457576https://pmc.ncbi.nlm.nih.gov/articles/PMC8457576/0
2021A Review on Preparation of Betulinic Acid and Its Biological ActivitiesHanghang LouPMC8468263https://pmc.ncbi.nlm.nih.gov/articles/PMC8468263/0
2021Betulinic acid in the treatment of tumour diseases: Application and research progressWenkai Jiang—https://www.sciencedirect.com/science/article/pii/S07533322210077330
2021Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice—https://www.sciencedirect.com/science/article/abs/pii/S15675769210084680
2021Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic PotentialSo Young KimPMC7961550https://pmc.ncbi.nlm.nih.gov/articles/PMC7961550/0
2021The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosisCheol ParkPMC8118407https://pmc.ncbi.nlm.nih.gov/articles/PMC8118407/0
2020Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling PathwayLijuan ZhuPMC7551141https://pmc.ncbi.nlm.nih.gov/articles/PMC7551141/0
2020Effects and mechanisms of fatty acid metabolism-mediated glycolysis regulated by betulinic acid-loaded nanoliposomes in colorectal cancerGang WangPMC7640364https://pmc.ncbi.nlm.nih.gov/articles/PMC7640364/0
2020Betulinic acid triggers apoptosis and inhibits migration and invasion of gastric cancer cells by impairing EMT progressYun Chen—https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/cbf.35370
2019Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic PathwayYifeng ZhengPMC6721262https://pmc.ncbi.nlm.nih.gov/articles/PMC6721262/0
2019Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potentialAnna Hordyjewska—https://link.springer.com/content/pdf/10.1007/s11101-019-09623-1.pdf0
2019Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple MyelomaMin ShenPMC6590575https://pmc.ncbi.nlm.nih.gov/articles/PMC6590575/0
2019Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivoAnqi Zeng30910472https://pubmed.ncbi.nlm.nih.gov/30910472/0
2019Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathwayLin Jiao30684465https://pubmed.ncbi.nlm.nih.gov/30684465/0
2018Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in ratsMadhu Kaundal—https://www.researchgate.net/publication/325212773_Betulinic_acid_a_natural_PDE_inhibitor_restores_hippocampal_cAMPcGMP_and_BDNF_improve_cerebral_blood_flow_and_recover_memory_deficits_in_permanent_BCCAO_induced_vascular_dementia_in_rats0
2018Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modificationsPranesh Kumar—https://www.sciencedirect.com/science/article/abs/pii/S00243205183044290
2018Betulinic acid chemosensitizes breast cancer by triggering ER stress-mediated apoptosis by directly targeting GRP78Youli Cai—https://www.nature.com/articles/s41419-018-0669-80
2018Betulinic acid induces DNA damage and apoptosis in SiHa cells—https://www.sciencedirect.com/science/article/abs/pii/S13835718173030780
2017Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cellsTao Xu—https://www.spandidos-publications.com/10.3892/ijmm.2017.31630
2017Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer modelsAn-Qi ZengPMC5790500https://pmc.ncbi.nlm.nih.gov/articles/PMC5790500/0
2017Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 SignalingHuan ShenPMC7841107https://pmc.ncbi.nlm.nih.gov/articles/PMC7841107/0
2017Down-regulation of NOX4 by betulinic acid protects against cerebral ischemia-reperfusion in micePei Lu—https://www.researchgate.net/publication/320735510_Down-regulation_of_NOX4_by_betulinic_acid_protects_against_cerebral_ischemia-reperfusion_in_mice0
2016Betulinic acid and the pharmacological effects of tumor suppressionXia Zhang—https://www.spandidos-publications.com/10.3892/mmr.2016.57920
2016Multiple molecular targets in breast cancer therapy by betulinic acidRunlan Luo27810789https://pubmed.ncbi.nlm.nih.gov/27810789/0
2015Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer TherapyMohamed Ali-Seyed26535952https://pubmed.ncbi.nlm.nih.gov/26535952/0
2014Cardioprotective Effect of Betulinic Acid on Myocardial Ischemia Reperfusion Injury in RatsAnzhou XiaPMC4055472https://pmc.ncbi.nlm.nih.gov/articles/PMC4055472/0
2014Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa CellsTao XuPMC4141803https://pmc.ncbi.nlm.nih.gov/articles/PMC4141803/0
2014Glycolytic Switch in Response to Betulinic Acid in Non-Cancer CellsElke H. Heiss—https://journals.plos.org/plosone/article?id=10.1371/journal.pone.01156830
2011Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factorsSudhakar Chintharlapalli—https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-3710
2010Betulinic acid, a natural compound with potent anticancer effectsFranziska B Mullauer—https://pubmed.ncbi.nlm.nih.gov/20075711/0
2009Betulinic acid: a natural product with anticancer activitySimone Fulda19065582https://pubmed.ncbi.nlm.nih.gov/19065582/0
2008Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapyHubert Kasperczyk16007147https://pubmed.ncbi.nlm.nih.gov/16007147/0
2008Betulinic Acid for Cancer Treatment and PreventionSimone FuldaPMC2658785https://pmc.ncbi.nlm.nih.gov/articles/PMC2658785/0
2007Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factorsSudhakar Chintharlapalli17363604https://pubmed.ncbi.nlm.nih.gov/17363604/0
2006Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cellsWojciech Rzeski16964520https://pubmed.ncbi.nlm.nih.gov/16964520/0
2006Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cellsWojciech Rzeski16964520https://pubmed.ncbi.nlm.nih.gov/16964520/0