Ursolic acid / AMPK 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)
AMPK, adenosine monophosphate-activated protein kinase: Click to Expand ⟱
Source:
Type:
AMPK: guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways.

-Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation.


AMPK activators:
-metformin or AICAR
-Resveratrol: activate AMPK indirectly
-Berberine
-Quercetin: may stimulate AMPK
-EGCG: thought to activate AMPK
-Curcumin: may activate AMPK

-Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models.
-Alpha-Lipoic Acid (ALA): associated with AMPK activation
Scientific Papers found: Click to Expand⟱
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↑,
2350- UA,    Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Akt↓, Glycolysis↓, HK2↓, PKM2↓, ATP↓, lactateProd↓, AMPK↑, TumAuto↑, Apoptosis↑, ERK↓, MMP↓, NO↑, ROS↑, DNAdam↑,
119- UA,  CUR,  RES,    Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, p‑STAT3↓, Src↓, AMPK↑, GlutMet↑, TCA↑, glut↓,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 1,   ROS⇅, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 3,   FAO↑, 1,   FASN↓, 1,   glut↓, 1,   GlutMet↑, 1,   Glycolysis↓, 1,   HK2↓, 2,   lactateProd↓, 2,   PKM2↓, 2,   TCA↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 1,   JNK↑, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNAdam↑, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   p‑ERK↓, 1,   Src↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,  

Migration ⓘ

CD31↓, 1,   Ki-67↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   NO↑, 2,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,  
Total Targets: 41

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   SOD↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: AMPK, adenosine monophosphate-activated protein kinase
3 Ursolic acid
1 Curcumin
1 Resveratrol
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#:9  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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