Database Query Results : Betulinic acid, , GlucoseCon

BetA, Betulinic acid: Click to Expand ⟱
Features:
Betulinic acid "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.
-Betulinic acid is a naturally occurring pentacyclic triterpenoid
-vitro concentrations range from 1–100 µM, in vivo studies in rodents have generally used doses from 10–100 mg/kg
Precursor: Betulin, via oxidation at C-28
Lipophilicity: High (poor aqueous solubility)
-half-life reports vary 3-5 hrs?. Reported half-life varies by formulation and species; several studies report multi-hour systemic persistence.
BioAv -hydrophobic molecule with relatively poor water solubility. 
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

Pathways:
- often induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells(Often associated with reduced redox buffering capacity in tumor cells (e.g., GSH depletion); NRF2 direction model-dependent.): NRF2↓, SOD↓, GSH↓
- May Raise AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑ Reports suggest relative sparing of normal cells and preservation of antioxidant capacity in some models
- lowers Inflammation : NF-kB↓(typ), COX2↓, p38↓ (context-dependent; often stress-activated), Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : P53↑, HSP↓(model-dependent), Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis (secondary to mitochondrial stress) ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, GRP78↑(ER stress), GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells in some studies : CSC↓, GLi1↓, β-catenin↓, OCT4↓,
- Others: PI3K↓(typ), AKT↓(typ), JAK↓, STAT↓, β-catenin↓, AMPK↓(AMPK is often activated during metabolic stress), ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Intrinsic apoptosis (mitochondrial-mediated) ↑ mitochondria depolarization; ↑ cytochrome-c; ↑ caspase-9/3 activation ↔ limited activation (higher exposure required) R, G Execution of apoptosis Betulinic acid (BA) is well known to engage the intrinsic apoptotic cascade, typically downstream of redox and signaling perturbations.
2 ROS / redox stress ↑ ROS (P→R) ↔ basal or antioxidant adaptation in some contexts P, R Stress induction Many studies report ROS elevation in tumor cells exposed to BA; the direction and magnitude vary by cell type and exposure.
3 Mitochondrial permeability transition / ΔΨm loss ΔΨm ↓ (R→G) ↔ maintained R, G Mitochondrial failure Often observed as an early event preceding caspase activation in apoptosis studies.
4 PI3K / AKT / mTOR survival axis ↓ PI3K/AKT signaling; ↓ phospho-mTOR ↔ R, G Survival/growth suppression Betulinic acid often downregulates pro-survival kinase signaling, sensitizing cells to apoptosis and cytostasis.
5 NF-κB signaling ↓ NF-κB activity ↔ R, G Pro-survival/inflammatory transcription suppression Reduction in NF-κB activity limits pro-survival gene expression; supports sensitization to stressors.
6 MAPK re-wiring (JNK / ERK / p38) Stress-MAPK shifts; JNK/p38 often ↑; ERK context-dependent ↔ P, R Early stress signaling MAPK responses vary by model, with stress-associated p38/JNK often activated and ERK modulation variable.
7 Cell-cycle checkpoints (p21, p27, cyclins) ↑ p21/p27; ↑ G1/S or G2/M arrest ↔ G Proliferation arrest BA often induces cell-cycle blockade, slowing proliferation before apoptosis commitment.
8 Angiogenic signaling (VEGF & related) ↓ VEGF; anti-angiogenic outputs ↔ G Anti-angiogenic support Typically seen at the level of reduced pro-angiogenic factor expression or secretion in longer-term assays.
9 EMT / invasion / migration programs (MMPs) ↓ MMP2/MMP9; ↓ migration/invasion ↔ G Anti-invasive phenotype Often measured as reduced invasive capacity and decreased expression of EMT markers in later time points.
10 Autophagy modulation ↑ LC3-II; ↑ autophagic flux (model dependent) ↔ G Adaptive clearance / cell fate shift BA can modulate autophagy, which may either sensitize cells to death pathways or reflect adaptive stress responses.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (primary/physical-chemical effects; rapid kinase/redox signaling)
  • R: 30 min–3 hr (acute redox and stress-response activation)
  • G: >3 hr (gene-regulatory adaptation and phenotypic outcomes)
GlucoseCon, Glucose Consumption: Click to Expand ⟱
Source:
Type:
Glucose consumption is often elevated in cancer cells due to an increased reliance on glycolysis for energy production, even in the presence of oxygen. This phenomenon, known as the Warburg effect, is a metabolic shift that allows cancer cells to rapidly proliferate and survive in nutrient-poor environments.

The increased glucose consumption in cancer cells can be detected using positron emission tomography (PET) scans, which measure the uptake of a glucose analog labeled with a radioactive tracer.
Scientific Papers found: Click to Expand⟱
2727- BetA,    Betulinic acid in the treatment of breast cancer: Application and mechanism progress
- Review, BC, NA
mt-ROS↑, Its mechanisms mainly include inducing mitochondrial oxidative stress, regulating specific protein (Sp) transcription factors, inhibiting breast cancer metastasis, inhibiting glucose metabolism and NF-κB pathway.
Sp1/3/4↓, By triggering the degradation of Sp1, Sp3, and Sp4, betulinic acid reduces the transcriptional activity of these factors
TumMeta↓,
GlucoseCon↓,
NF-kB↓,
ChemoSen↑, BA can also increase the sensitivity of breast cancer cells to other chemotherapy drugs such as paclitaxel and reduce its toxic side effects.
chemoP↑,
m-Apoptosis↑, variety of mechanisms, including inducing mitochondrial apoptosis, inhibiting topoisomerase
TOP1↓, betulinic acid may inhibit the ability of topoisomerase I or II to properly cleave and re-ligate DNA strands.

943- BetA,    Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
Glycolysis↓,
lactateProd↓,
GlucoseCon↓,
ECAR↓,
cMyc↓,
LDHA↓,
p‑PDK1↓,
PDK1↓,
Cav1↑, Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation
*Glycolysis↑, BA could lead to increased glycolysis in mouse embryonic fibroblasts by activating LKB1/AMPK pathway, whereas we found that BA inhibited aerobic glycolysis in breast cancer cells by modulating Cav-1/NF-κB/c-Myc signaling
selectivity↑,
OCR↓, OCR parameters including the basal respiration, maximal respiration and spare respiratory capacity were also simultaneously inhibited
OXPHOS↓, implying that the activity of mitochondrial oxidative phosphorylation (OXPHOS) chain was also suppressed by BA

2739- BetA,    Glycolytic Switch in Response to Betulinic Acid in Non-Cancer Cells
- in-vitro, Nor, HUVECs - in-vitro, Nor, MEF
*Glycolysis↑, BA elevates the rates of cellular glucose uptake and aerobic glycolysis in mouse embryonic fibroblasts with concomitant reduction of glucose oxidation.
*GlucoseCon↑, BA increases cellular glucose uptake
*Apoptosis↓, Without eliciting signs of obvious cell death BA leads to compromised mitochondrial function, increased expression of mitochondrial uncoupling proteins (UCP) 1 and 2, and liver kinase B1 (LKB1)-dependent activation AMP-activated protein kinase.
*UCP1↓,
*AMPK↑, AMPK activation accounts for the increased glucose uptake and glycolysis which in turn are indispensable for cell viability upon BA treatment.
GLUT1↑, The expression of glucose transporter GLUT1 was elevated upon BA treatment for 16 h
mt-ROS↑, We observed increased production of mitochondrial ROS (Fig. 4A) and elevated expression of uncoupling proteins UCP1 and UCP2 in BA-treated MEF

2740- BetA,    Effects and mechanisms of fatty acid metabolism-mediated glycolysis regulated by betulinic acid-loaded nanoliposomes in colorectal cancer
- in-vitro, CRC, HCT116
TumCP↓, BA-NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti-CRC function of BA-NLs.
Glycolysis↓,
HK2↓, HK2, PFK-1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA-NLs, which play key roles in the inhibition of glycolysis and fatty acid-mediated production of pyruvate and lactate.
PFK1↓,
PKM2↓,
ACSL1↓,
CPT1A↓,
FASN↓,
FAO↓, Significant reduction of FAO was detected in BA-NL-treated HCT116 cells
GlucoseCon↓, glucose uptake in HCT116 cells was significantly decreased by BA-NLs
lactateProd↓, lactic acid secretion was significantly suppressed in HCT116 cells treated with BA-NLs


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

OXPHOS↓, 1,   mt-ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

m-Apoptosis↑, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TOP1↓, 1,  

Migration ⓘ

TumCP↓, 1,   TumMeta↓, 1,  

Barriers & Transport ⓘ

GLUT1↑, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   selectivity↑, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,  
Total Targets: 29

Pathway results for Effect on Normal Cells:


Mitochondria & Bioenergetics ⓘ

UCP1↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   GlucoseCon↑, 1,   Glycolysis↑, 2,  

Cell Death ⓘ

Apoptosis↓, 1,  
Total Targets: 5

Scientific Paper Hit Count for: GlucoseCon, Glucose Consumption
4 Betulinic acid
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:42  Target#:623  State#:%  Dir#:%
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