Ursolic acid / Casp3 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)
Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
5021- UA,    Anticancer effect of ursolic acid via mitochondria-dependent pathways
- Review, Var, NA
Inflam↓, TNF-α↓, IL6↓, IL17↓, NF-kB↓, COX2↓, *AntiDiabetic↑, *hepatoP↑, ALAT↓, AST↓, TumCP↓, Apoptosis↑, TumCCA↑, TumAuto↑, tumCV↓, TumCMig↓, Glycolysis↓, ATP↓, lactateProd↓, HK2↓, PKA↓, COX2↓, mtDam↑, Casp3↑, Casp8↑, Casp9↑, Akt↓, ROS↑, MMP↓, P53↑,
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↑,
1020- UA,    Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/β-Catenin Pathway
- in-vitro, Melanoma, RPMI-8226
β-catenin/ZEB1↓, TCF↓, cMyc↓, cycD1/CCND1↓, TumCP↓, TumCCA↑, Apoptosis↑, cl‑Casp3↑, cl‑PARP↑, Casp7↑,

Showing Research Papers: 1 to 4 of 4

* 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 ⓘ

antiOx↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   cMyc↓, 1,   FAO↑, 1,   FASN↓, 1,   Glycolysis↓, 1,   HK2↓, 2,   lactateProd↓, 2,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   Bcl-2↓, 2,   Bcl-xL↓, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp8↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   JNK↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   P21↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,   STAT3↓, 1,   TCF↓, 1,  

Migration ⓘ

CD31↓, 1,   Ki-67↓, 1,   PKA↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   NO↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL17↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 2,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   neuroP↑, 1,  
Total Targets: 58

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 ⓘ

AntiDiabetic↑, 1,   cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 2,   neuroP↑, 1,  
Total Targets: 19

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
4 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#:42  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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