Betulinic acid / ROS Cancer Research Results

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)

Betulinic acid — Betulinic acid is a naturally occurring lupane-type pentacyclic triterpenoid with broad experimental anticancer activity, especially against melanoma, neuroectodermal, glioma, breast, colorectal, and other solid-tumor models. It is a natural-product small molecule, usually abbreviated BA or BetA, and is found in several plants, classically birch bark, with semi-synthesis commonly starting from betulin. A distinguishing feature is preferential induction of tumor-cell death through direct mitochondrial injury with relative sparing of many non-neoplastic cells in preclinical systems. Its main translational limitation is very poor aqueous solubility with correspondingly weak oral/systemic developability unless formulation or derivatization is used.

Primary mechanisms (ranked):

  1. Direct mitochondrial membrane permeabilization with intrinsic apoptosis activation
  2. Mitochondrial ROS increase with collapse of mitochondrial membrane potential and cytochrome c release
  3. ER-stress and unfolded-protein-response activation, including GRP78-linked stress signaling
  4. Suppression of NF-κB and other pro-survival transcriptional programs, including Sp-family signaling in some models
  5. Cell-cycle arrest with reduced cyclin/CDK signaling
  6. Anti-migratory and anti-invasive effects via EMT, FAK, ROCK1, MMP, and cytoskeletal remodeling pathways
  7. Secondary metabolic suppression of aerobic glycolysis and hypoxia-response signaling in susceptible models
  8. Adjunct sensitization to chemo- or radiotherapy in selected preclinical settings

Bioavailability / PK relevance: Betulinic acid is highly lipophilic and poorly water-soluble, which strongly limits oral absorption and systemic exposure. PK behavior is formulation-dependent, and much of the translational literature focuses on nanoparticles, liposomes, micelles, conjugates, or topical delivery rather than conventional oral dosing.

In-vitro vs systemic exposure relevance: Many in-vitro anticancer studies use low-to-mid micromolar concentrations, which are often difficult to reproduce reliably in vivo with unformulated parent betulinic acid. Accordingly, mechanistic findings are useful biologically, but direct concentration matching to standard oral/systemic use is often poor unless enhanced-delivery systems are used.

Clinical evidence status: Strong preclinical and formulation-development literature; very limited human oncology evidence. Cancer-facing clinical development appears to remain early-phase/topical, with orphan designation for topical metastatic melanoma but no FDA approval for that indication. Betulinic acid itself is not an established approved anticancer drug.

-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

Mechanistic profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial permeabilization ↑ MOMP, ↓ ΔΨm, ↑ cytochrome c release, ↑ apoptosis ↔ / milder effect P-R Core tumor-selective death trigger Best-supported central mechanism; helps explain activity in apoptosis-competent but therapy-resistant tumors.
2 Mitochondrial ROS increase ↑ ROS ↔ / possible antioxidant sparing (context-dependent) P-R Amplifies mitochondrial stress and death signaling ROS appears mechanistically relevant in many tumor models, but not every study makes it the dominant initiating event.
3 Caspase axis and caspase-independent death ↑ caspase-9, ↑ caspase-3, ↑ PARP cleavage; caspase-independent death also reported ↔ R-G Executes apoptosis after mitochondrial injury BA can still kill some tumor cells when classical caspase execution is partly blocked, indicating non-canonical death contribution.
4 ER stress / UPR / GRP78 ↑ ER stress, ↑ UPR, ↑ GRP78 stress signaling ↔ R-G Links proteostatic stress to apoptosis and metastasis suppression Especially relevant in breast and gastric cancer models; may also connect to metabolic suppression and chemosensitization.
5 NF-κB survival signaling ↓ NF-κB ↔ / ↓ inflammatory tone R-G Reduces survival, inflammatory, and resistance programs Common downstream convergence node across several tumor types.
6 Cell-cycle machinery ↓ cyclin D1, ↓ CDK2, ↓ CDK4, ↑ cell-cycle arrest ↔ G Slows proliferation Usually supportive rather than primary; often follows stress and survival-pathway disruption.
7 EMT / invasion / matrix remodeling ↓ EMT, ↓ FAK, ↓ ROCK1, ↓ MMP2, ↓ MMP9, ↓ migration, ↓ invasion ↔ G Antimetastatic effect Consistent with reduced motility and invasive phenotype in multiple solid-tumor models.
8 Glycolysis ↓ glucose uptake, ↓ lactate, ↓ ECAR, ↓ HK2, ↓ PKM2, ↓ LDHA ↔ G Secondary metabolic suppression Not the universal initiating mechanism; appears important in selected breast-cancer and GRP78-linked systems.
9 HIF-1α hypoxia axis ↓ HIF-1α, ↓ VEGF, ↓ GLUT1, ↓ PDK1 ↔ G Reduces hypoxic adaptation and angiogenic drive Relevant in hypoxic tumor biology and helps explain antiangiogenic/metabolic effects in some models.
10 NRF2 / antioxidant buffering ↓ NRF2 or ↓ redox buffering (model-dependent) ↔ / possible preservation of antioxidant tone (context-dependent) R-G May widen tumor redox vulnerability Direction is not uniform across all models; safer to treat this as contextual rather than universally core.
11 Ca²⁺ stress ↑ Ca²⁺ (context-dependent) ↔ P-R Supports organelle stress and apoptotic signaling Usually part of the broader mitochondrial/ER stress network rather than a stand-alone primary target.
12 Radiosensitization or Chemosensitization ↑ sensitivity to radiation or selected drugs Unclear G Adjunct leverage Preclinical evidence supports additive or sensitizing effects with irradiation and with some chemotherapy settings, but this is not yet clinically established.
13 Clinical Translation Constraint Poor solubility and limited systemic exposure constrain reproducibility Same formulation constraint G Delivery bottleneck Main barrier is not lack of mechanistic richness but drug-like exposure; translation currently depends heavily on formulation, derivatization, or topical/local use.

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)
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
2760- BetA,    A Review on Preparation of Betulinic Acid and Its Biological Activities
- Review, Var, NA - Review, Stroke, NA
AntiTum↑, Cyt‑c↑, Smad1↑, Sepsis↓, NF-kB↓, ICAM-1↓, MCP1↓, MMP9↓, COX2↓, PGE2↓, ERK↓, p‑Akt↓, *ROS↓, *LDH↓, *hepatoP↑, *SOD↑, *Catalase↑, *GSH↑, *AST↓, *ALAT↓, *RenoP↑, *ROS↓, *α-SMA↓,
2759- BetA,    Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies
- Review, Var, NA
chemoPv↑, ChemoSen↑, *Inflam↓, *NRF2↑, *NF-kB↓, *COX2↓, ROS↑, MMP↓, Sp1/3/4↓, VEGF↓,
2758- BetA,    Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway
- in-vivo, Nor, NA
*ROS↓, *MDA↓, *SOD↑, *GSH↑, *p‑p38↓, *p‑JNK↓, *p‑ERK↓, *NRF2↑, *HO-1↑, *MAPK↓, *heparanase↑, *antiOx↑,
2756- BetA,    Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway
- in-vitro, HCC, HUH7 - in-vitro, HCC, H1299
TumCP↓, ROS↑, antiOx↓, TumCG↓, TumCMig↓, NRF2↓, GPx4↓, HO-1↓, NCOA4↑, FTH1↓, Ferritin↑, Ferroptosis↑, GSH↓, MDA↓,
2753- BetA,    Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cells
- in-vitro, Cerv, HeLa
PI3K↓, p‑Akt↓, ROS↑, TumCCA↑, p27↑, P21↑, mt-Apoptosis↑, BAD↑, Casp9↑, MMP↓, eff↓,
2752- BetA,    Betulinic acid: a natural product with anticancer activity
- Review, Var, NA
selectivity↑, ChemoSen↑, RadioS↑, MMP↓, cl‑Casp3↑, Cyt‑c↑, ROS↑, NF-kB↑, TOP1↓,
2747- BetA,    Betulinic acid, a natural compound with potent anticancer effects
- Review, Var, NA
selectivity↑, Cyt‑c↑, *toxicity↓, TOP1↓, NF-kB↓, ROS↑, RadioS↑, ChemoSen↑,
5591- BetA,    Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment
- Review, BC, NA
BioAv↓, BioAv↑, selectivity↑, eff↑, angioG↓, *antiOx↑, *Inflam↓, MMP↓, Bcl-2↓, BAX↑, Casp9↑, Casp3↑, GRP78/BiP?, ER Stress↑, PERK↑, CHOP↑, ChemoSen↑, SESN2↑, ROS↑, MOMP↓, MAPK↑, Cyt‑c↑, AIF↑, STAT3↓, FAK↓, TIMP2↑, TumCMig↓, TumCI↓, Sp1/3/4↓, TumCCA↑, DNAdam↑,
2746- BetA,    Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivo
- in-vitro, CRC, HCT116 - in-vivo, CRC, NA
TumCG↓, BAX↑, Bcl-2↓, ROS↑, MMP↓, TIMP2↑, TumVol↓,
5583- BetA,    Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells
- vitro+vivo, NA, NA
ROS↑, Bcl-2↓, BAX↑, TOP1↝, eff↝, toxicity↓, toxicity↓, selectivity↑,
5582- BetA,    Targeting mitochondrial apoptosis by betulinic acid in human cancers
- Review, Var, NA
Apoptosis↑, MMP↓, Cyt‑c↑, ROS↑, NF-kB↑, angioG↓, mtDam↑, TOP1↓, selectivity↑, ChemoSen↑, TumCG↓, chemoPv↑, RadioS↑,
4273- BetA,    Betulinic 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 rats
- in-vivo, NA, NA
*neuroP↑, *BDNF↑, *ROS↓, *Inflam↓, *cognitive↑,
2720- BetA,    Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo
- in-vitro, Cerv, HeLa
Keap1↝, ROS↑, Ca+2↑, Beclin-1↓, GRP78/BiP↑, LC3II↑, p62↑, ERStress↑, TumAuto↑,
2727- BetA,    Betulinic acid in the treatment of breast cancer: Application and mechanism progress
- Review, BC, NA
mt-ROS↑, Sp1/3/4↓, TumMeta↓, GlucoseCon↓, NF-kB↓, ChemoSen↑, chemoP↑, m-Apoptosis↑, TOP1↓,
2726- BetA,    Betulinic acid induces DNA damage and apoptosis in SiHa cells
- in-vitro, Cerv, SiHa
tumCV↓, DNAdam↑, MMP↓, ROS↑, TumCCA↑, TOP1↓,
2725- BetA,    Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice
- in-vivo, Nor, NA
*RenoP↑, *SOD?, *Catalase↑, *GSH↑, *ROS↓, *MDA↓, *IL1β↓, *TNF-α↓, *IL10↓, *IL6↑, *NRF2↑,
2724- BetA,    Down-regulation of NOX4 by betulinic acid protects against cerebral ischemia-reperfusion in mice
- in-vivo, Nor, NA - in-vivo, Stroke, NA
AntiTum↑, *Inflam↓, *ROS↓, *NOX4↓, *Apoptosis↓, neuroP↑,
2723- BetA,    Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation
- in-vitro, BC, MDA-MB-231
Apoptosis↑, tumCV↓, ROS↑,
2722- BetA,    Betulinic Acid for Cancer Treatment and Prevention
- Review, Var, NA
MMP↓, Cyt‑c↑, cl‑Casp3↑, cl‑Casp8↑, ROS↑, NF-kB↑, TOP1↓,
2721- BetA,    Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa Cells
- in-vitro, Cerv, HeLa
ROS↑, Dose↝, Bcl-2↓, BAX↑, ER Stress↑,
2729- BetA,    Betulinic acid in the treatment of tumour diseases: Application and research progress
- Review, Var, NA
ChemoSen↑, mt-ROS↑, STAT3↓, NF-kB↓, selectivity↑, *toxicity↓, eff↑, GRP78/BiP↑, MMP2↓, P90RSK↓, TumCI↓, EMT↓, MALAT1↓, Glycolysis↓, AMPK↑, Sp1/3/4↓, Hif1a↓, angioG↓, NF-kB↑, NF-kB↓, MMP↓, Cyt‑c↑, Casp9↑, Casp3↑, RadioS↑, PERK↑, CHOP↑, *toxicity↓,
2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24/HTB-9 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, Apoptosis↑, TumCCA↑, CycB/CCNB1↓, cycA1/CCNA1↓, CDK2↓, CDC25↓, mtDam↑, BAX↑, cl‑PARP↑, Casp3↑, Casp8↑, Casp9↑, Snail↓, Slug↓, MMP9↓, selectivity↑, MMP↓, ROS∅, TumCMig↓, TumCI↓,
2718- BetA,    The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis
- in-vitro, AML, U937
TumCCA↑, Apoptosis↑, i-ROS↑, cycA1/CCNA1↓, CycB/CCNB1↓, P21↑, Cyt‑c↑, MMP↓, Bax:Bcl2↑, Casp9↑, Casp3↑, PARP↓, eff↓, *antiOx↑, *Inflam↓, *hepatoP↑, selectivity↑, NF-kB↓, *ROS↓,
2717- BetA,    Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma
- in-vitro, Melanoma, U266 - in-vivo, Melanoma, NA - in-vitro, Melanoma, RPMI-8226
Apoptosis↑, TumCCA↑, MMP↓, ROS↑, eff↓, NF-kB↓, Cyt‑c↑, Casp3↑, Casp8↑, Casp9↑, cl‑PARP1↑, MDA↑, SOD↓, SOD2↓, GCLM↓, GSTA1↓, FTH1↓, GSTs↓, TumVol↓,
2716- BetA,    Cellular and molecular mechanisms underlying the potential of betulinic acid in cancer prevention and treatment
- Review, Var, NA
AntiCan↑, TumCD↑, TumCCA↑, ROS↑, NF-kB↓, Bcl-2↓, Half-Life↝, GLUT1↓, VEGF↓, PDK1↓,
2737- BetA,    Multiple molecular targets in breast cancer therapy by betulinic acid
- Review, Var, NA
TumCP↓, Cyc↓, TOP1↓, TumCCA↑, angioG↓, NF-kB↓, Sp1/3/4↓, VEGF↓, MMPs↓, ChemoSen↑, eff↑, MMP↓, ROS↑, Bcl-2↓, Bcl-xL↓, Mcl-1↓, lipid-P↑, RadioS↑, eff↑,
2745- BetA,    Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors
- in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vivo, NA, NA
Apoptosis↑, TumCG↓, Sp1/3/4↓, survivin↓, VEGF↓, p65↓, EGFR↓, cycD1/CCND1↓, ROS↑, MMP↓,
2744- BetA,    Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential
- Review, Var, NA
Apoptosis↓, TumCCA↑, Casp9↑, Casp3↑, Casp7↑, cl‑PARP↑, MMP↓, ROS↑, TOP1↓, NF-kB↓,
2743- BetA,    Betulinic acid and the pharmacological effects of tumor suppression
- Review, Var, NA
ROS↑, MMP↓, Cyt‑c↑, Apoptosis↑, TumCCA↑, Sp1/3/4↓, STAT3↓, NF-kB↓, EMT↓, TOP1↓, MAPK↑, p38↑, JNK↑, Casp↑, Bcl-2↓, BAX↑, VEGF↓, LAMs↓,
2739- BetA,    Glycolytic Switch in Response to Betulinic Acid in Non-Cancer Cells
- in-vitro, Nor, HUVECs - in-vitro, Nor, MEF
*Glycolysis↑, *GlucoseCon↑, *Apoptosis↓, *UCP1↓, *AMPK↑, GLUT1↑, mt-ROS↑,
2738- BetA,    Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549 - in-vivo, NA, NA
TumCI↓, TumCMig↓, Glycolysis↓, lactateProd↓, GRP78/BiP↑, ER Stress↑, PERK↑, p‑eIF2α↑, β-catenin/ZEB1↓, cMyc↓, ROS↑, angioG↓, Sp1/3/4↓, DNAdam↑, TOP1↓, TumMeta↓, MMP2↓, MMP9↓, N-cadherin↓, Vim↓, E-cadherin↑, EMT↓, LDHA↓, p‑PDK1↓, PDK1↓, ECAR↓, OCR↓, Hif1a↓, STAT3↓,
2736- BetA,  Chemo,    Multifunctional 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 Metastasis
- Review, Var, NA
chemoPv↑, p‑STAT3↓, JAK1↓, JAK2↓, VEGF↓, EGFR↓, Cyt‑c↑, Diablo↑, AMPK↑, mTOR↓, Sp1/3/4↓, DNAdam↑, Gli1↓, GLI2↓, PTCH1↓, MMP2↓, MMP9↓, miR-21↓, SOD2↓, ROS↑, Apoptosis↑,
2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, Casp↑, p38↑, MAPK↓, JNK↓, VEGF↓, AIF↑, Cyt‑c↑, ROS↑, Ca+2↑, ATP↓, NF-kB↓, ATF3↓, TOP1↓, VEGF↓, survivin↓, Sp1/3/4↓, MMP↓, ChemoSen↑, selectivity↑, BioAv↓, BioAv↑, BioAv↑, BioAv↑, BioAv↑,
2734- BetA,    Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW480
tumCV↓, HSP70/HSPA5⇅, ROS↑, cl‑Casp3↑, mt-Apoptosis↑, Dose↝,
2733- BetA,    Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling
- in-vitro, Oral, KB - in-vivo, NA, NA
TumCP↓, TumVol↓, mt-Apoptosis↑, Casp3↑, Casp9↑, BAX↑, Bcl-2↑, OCR↓, TumCCA↑, ROS↑, eff↓, P53↑, STAT3↓, cycD1/CCND1↑,
2731- BetA,    Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives
- Review, GBM, NA - Review, Park, NA - Review, AD, NA
BBB↑, *GSH↑, *Catalase↑, *motorD↑, *neuroP↑, *cognitive↑, *ROS↓, *antiOx↑, *Inflam↓, MMP↓, STAT3↓, NF-kB↓, Sp1/3/4↓, TOP1↓, EMT↓, Hif1a↓, VEGF↓, ChemoSen↑, RadioS↑, BioAv↓,
2730- BetA,    Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells
- in-vitro, Bladder, T24/HTB-9
tumCV↓, TumCP↓, TumCMig↓, Casp↑, TumAuto↑, LC3B-II↑, p‑AMPK↑, mTOR↓, BMI1↓, ROS↑, eff↓,

Showing Research Papers: 1 to 37 of 37

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 37

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ATF3↓, 1,   Ferroptosis↑, 1,   GCLM↓, 1,   GPx4↓, 1,   GSH↓, 1,   GSTA1↓, 1,   GSTs↓, 1,   HO-1↓, 1,   Keap1↝, 1,   lipid-P↑, 1,   MDA↓, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↑, 26,   ROS∅, 1,   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,   MMP↓, 18,   mtDam↑, 2,   OCR↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   p‑AMPK↑, 1,   cMyc↓, 1,   ECAR↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   lactateProd↓, 1,   LDHA↓, 1,   PDK1↓, 2,   p‑PDK1↓, 1,  

Cell Death ⓘ

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

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 11,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   p‑eIF2α↑, 1,   ER Stress↑, 3,   ERStress↑, 1,   GRP78/BiP?, 1,   GRP78/BiP↑, 3,   HSP70/HSPA5⇅, 1,   PERK↑, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   LC3B-II↑, 1,   LC3II↑, 1,   p62↑, 1,   SESN2↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   Cyc↓, 1,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 1,   cycD1/CCND1↑, 1,   P21↑, 2,   TumCCA↑, 11,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   EMT↓, 4,   ERK↓, 1,   Gli1↓, 1,   mTOR↓, 2,   P90RSK↓, 1,   PI3K↓, 1,   PTCH1↓, 1,   STAT3↓, 6,   p‑STAT3↓, 1,   TOP1↓, 12,   TOP1↝, 1,   TumCG↓, 4,  

Migration ⓘ

Ca+2↑, 2,   E-cadherin↑, 1,   FAK↓, 1,   GLI2↓, 1,   LAMs↓, 1,   MALAT1↓, 1,   MMP2↓, 3,   MMP9↓, 4,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   Smad1↑, 1,   Snail↓, 1,   TIMP2↑, 2,   TumCI↓, 4,   TumCMig↓, 5,   TumCP↓, 4,   TumMeta↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   EGFR↓, 2,   Hif1a↓, 3,   VEGF↓, 9,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 1,   GLUT1↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   ICAM-1↓, 1,   JAK1↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 13,   NF-kB↑, 4,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 5,   ChemoSen↑, 10,   Dose↝, 2,   eff↓, 5,   eff↑, 4,   eff↝, 1,   Half-Life↝, 1,   RadioS↑, 6,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   Ferritin↑, 1,  

Functional Outcomes ⓘ

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

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 169

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

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

Mitochondria & Bioenergetics ⓘ

UCP1↓, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,  

Migration ⓘ

heparanase↑, 1,   α-SMA↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↑, 1,   Inflam↓, 6,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

cognitive↑, 2,   hepatoP↑, 2,   motorD↑, 1,   neuroP↑, 2,   RenoP↑, 2,   toxicity↓, 3,  
Total Targets: 41

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
37 Betulinic acid
1 Chemotherapy
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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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