Ursolic acid / Bcl-2 Cancer Research Results

UA, Ursolic acid: Click to Expand ⟱
Features:
Natural compound found in apples and rosemary.
Ursolic acid (UA) is a pentacyclic triterpenoid found in many plants (notably apple peel, rosemary, thyme, holy basil, and other herbs). In cancer models it is best described as a multi-target signaling modulator with prominent effects on NF-κB inflammation/survival transcription, STAT3, PI3K/AKT/mTOR, and MAPK pathways, with downstream outcomes including cell-cycle arrest, apoptosis, anti-angiogenesis, and reduced invasion/EMT. A practical translational constraint is poor aqueous solubility and low oral bioavailability, so many strong in-vitro µM effects may not map cleanly to typical oral exposure without formulation.

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 NF-κB inflammatory / survival transcription NF-κB ↓; COX-2/iNOS/cytokines/Bcl-2 family/MMPs ↓ (reported) Inflammation tone ↓ (context) R, G Anti-inflammatory + anti-survival transcription One of the most frequently reported UA effects across tumor models; downstream impacts include reduced pro-survival and pro-metastatic gene programs.
2 STAT3 axis (JAK/STAT3 signaling) STAT3 activity ↓ (reported); downstream targets ↓ ↔ R, G Oncogenic transcription suppression UA is often reported to suppress STAT3 signaling, contributing to reduced proliferation/survival signaling.
3 PI3K → AKT (± mTOR) survival axis PI3K/AKT ↓; mTORC1 tone ↓ (reported; model-dependent) ↔ R, G Growth/survival modulation Commonly listed mechanism; direction and strength vary by cell line and exposure.
4 MAPK re-wiring (ERK / JNK / p38) Stress-MAPK modulation (context-dependent) ↔ P, R, G Signal reprogramming JNK/p38 activation and ERK modulation are reported variably; avoid fixed arrows unless tied to a specific model.
5 Cell-cycle checkpoints (Cyclins/CDKs; p21/p27) Cell-cycle arrest ↑ (G1/S or G2/M; reported); Cyclin D1/CDKs ↓ (context) ↔ G Cytostasis Often downstream of NF-κB/STAT3/PI3K signaling suppression.
6 Intrinsic apoptosis (mitochondrial/caspase linked) Apoptosis ↑; Bax ↑; Bcl-2 ↓; caspases ↑ (reported) ↔ (generally less activation) G Cell death execution Common downstream endpoint; can be coupled to stress signaling and survival pathway suppression.
7 Angiogenesis signaling (VEGF / HIF-1α outputs) VEGF ↓; angiogenic outputs ↓ (reported) ↔ G Anti-angiogenic support Typically phenotype-level effects tied to NF-κB/PI3K/HIF programs.
8 Invasion / metastasis programs (MMPs / EMT) MMP2/MMP9 ↓; EMT markers ↓; migration/invasion ↓ (reported) ↔ G Anti-invasive phenotype Often downstream of NF-κB/STAT3 changes; not universal across all tumors.
9 ROS / redox modulation ROS direction variable; redox stress or buffering reported (context) Oxidative injury ↓ in some non-tumor stress models P, R, G Stress modulation UA is not a reliable “pro-oxidant killer”; redox effects depend on dose, model, and baseline oxidative state.
10 Bioavailability / formulation constraint Systemic exposure often limited (poor solubility) — — Translation constraint UA is highly lipophilic with poor aqueous solubility; many formulations (e.g., nanoparticles, phospholipid complexes) are explored to improve exposure.

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

  • P: 0–30 min (rapid signaling interactions)
  • R: 30 min–3 hr (acute stress-response + transcription signaling shifts)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
Bcl-2, B-cell CLL/lymphoma 2: Click to Expand ⟱
Source: HalifaxProj (inhibit) CGL-Driver Genes
Type: Antiapoptotic Oncogene
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.
Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.
Scientific Papers found: Click to Expand⟱
5020- UA,    Anticancer activity of ursolic acid on human ovarian cancer cells via ROS and MMP mediated apoptosis, cell cycle arrest and downregulation of PI3K/AKT pathway
- in-vitro, Ovarian, NA
tumCV↓, selectivity↑, BAX↑, Bcl-2↓, Apoptosis↑, ROS↑, TumCCA↑, Akt↓, PI3K↓,
5017- UA,    Ursolic acid disturbs ROS homeostasis and regulates survival-associated gene expression to induce apoptosis in intestinal cancer cells
- in-vitro, Cerv, INT-407 - in-vitro, CRC, HCT116
AntiCan↑, TumCG↓, ROS↑, Apoptosis↑, TumCMig↓, CTNNB1↓, Twist↓, Bcl-2↓, survivin↓, NF-kB↓, Sp1/3/4↓, BAX↑, P21↑, P53↑, eff↓, TumCMig↓,
3790- UA,    Therapeutic applications of ursolic acid: a comprehensive review and utilization of predictive tools
*Inflam↓, *antiOx↑, AntiCan↑, *neuroP↑, *hepatoP↑, *cardioP↑, *MMP↑, *ROS↓, *PGC-1α↑, *BDNF↑, *cognitive↑, Bcl-2↓, Cyt‑c↑, DR5↑, Casp9↑, Casp8↑, Casp3↑, TumCCA↑, *BioAv↓, *Dose↝, *Half-Life↓, *Half-Life↓,
2411- UA,    Ursolic acid in health and disease
- Review, Var, NA
Inflam↓, antiOx↑, NF-kB↓, Bcl-xL↓, Bcl-2↓, cycD1/CCND1↓, Ki-67↓, CD31↓, STAT3↓, EGFR↓, P53↑, P21↓, HK2↓, PKM2↓, ATP↓, lactateProd↓, p‑ERK↓, MMP↓, NO↑, ATM↑, Casp3↑, AMPK↑, JNK↑, FAO↑, FASN↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *GSTs↑, neuroP↑,
1310- UA,    Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells
- in-vitro, BC, MCF-7
GR↝, AP-1↝, cl‑PARP↑, Bcl-2↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   FAO↑, 1,   FASN↓, 1,   HK2↓, 1,   lactateProd↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 2,   Bcl-2↓, 5,   Bcl-xL↓, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   JNK↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↓, 1,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CTNNB1↓, 1,   p‑ERK↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

AP-1↝, 1,   CD31↓, 1,   Ki-67↓, 1,   TumCMig↓, 2,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   NO↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 2,  

Hormonal & Nuclear Receptors ⓘ

GR↝, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   neuroP↑, 1,  
Total Targets: 52

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   ROS↓, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   PGC-1α↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose↝, 1,   Half-Life↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 18

Scientific Paper Hit Count for: Bcl-2, B-cell CLL/lymphoma 2
5 Ursolic 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#:164  Target#:27  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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