Resveratrol / β-catenin/ZEB1 Cancer Research Results

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
4701- PTS,  RES,    Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene
- Review, Var, NA
CSCs↓, E-cadherin↑, NF-kB↓, EMT↓, GRP78/BiP↓, CD133↓, COX2↓, β-catenin/ZEB1↓, NOTCH↓,
3085- RES,    Resveratrol interrupts Wnt/β-catenin signalling in cervical cancer by activating ten-eleven translocation 5-methylcytosine dioxygenase 1
- in-vitro, Cerv, NA
TET1↑, Wnt↓, β-catenin/ZEB1↓,
4663- RES,    Exploring resveratrol’s inhibitory potential on lung cancer stem cells: a scoping review of mechanistic pathways across cancer models
- Review, Var, NA
*antiOx↑, *Inflam↓, *chemoPv↑, CSCs↓, Wnt↓, β-catenin/ZEB1↓, NOTCH↓, PI3K↓, Akt↓, mTOR↓, GSK‐3β↝, Snail↓, HH↓, p‑GSK‐3β↓, N-cadherin↓, EMT↓, CD133↓, CD44↓, ALDH1A1↓, OCT4↓, SOX4↓, Shh↓, Smo↓, Gli1↓, GLI2↓,
4662- RES,    A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H460
CSCs↓, CD133↓, OCT4↓, β-catenin/ZEB1↓, HER2/EBBR2↓, TumCP↓, PI3K↓, Akt↓, ALDH1A1↓, eff↑,
3098- RES,    Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers
- Review, Var, NA
NOTCH2↓, Wnt↓, β-catenin/ZEB1↓, p‑SMAD2↓, p‑SMAD3↓, PTCH1↓, Smo↓, Gli1↓, E-cadherin↑, NOTCH⇅, TAC?, NKG2D↑, DR4↑, survivin↓, DR5↑, BAX↑, p27↑, cycD1/CCND1↓, Bcl-2↓, STAT3↓, STAT5↓, JAK↓, DNAdam↑, γH2AX↑,
2981- RES,    Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways
- in-vitro, Colon, HT-29 - in-vitro, Colon, SW48
TumCCA↑, p27↑, cycD1/CCND1↓, TumCP↓, IGF-1R↓, Akt↓, Wnt↓, P53↑, Apoptosis↑, Sp1/3/4↓, cl‑PARP↑, β-catenin/ZEB1↓, MDM2↓,
2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, *BioAv↝, *Dose↝, *hepatoP↑, *neuroP↑, *AntiAg↑, *COX2↓, *antiOx↑, *ROS↓, *ROS↑, PI3K↓, Akt↓, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, NRF2↑, GPx↑, HO-1↑, BioEnh?, PTEN↑, ChemoSen↑, eff↑, mt-ROS↑, Warburg↓, Glycolysis↓, GlucoseCon↓, GLUT1↓, lactateProd↓, HK2↓, EGFR↓, cMyc↓, ROS↝, MMPs↓, MMP7↓, survivin↓, TumCP↓, TumCMig↓, TumCI↓,
2687- RES,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, NA, NA - Review, AD, NA
NF-kB↓, P450↓, COX2↓, Hif1a↓, VEGF↓, *SIRT1↑, SIRT1↓, SIRT2↓, ChemoSen⇅, cardioP↑, *memory↑, *angioG↑, *neuroP↑, STAT3↓, CSCs↓, RadioS↑, Nestin↓, Nanog↓, TP53↑, P21↑, CXCR4↓, *BioAv↓, EMT↓, Vim↓, Slug↓, E-cadherin↑, AMPK↑, MDR1↓, DNAdam↑, TOP2↓, PTEN↑, Akt↓, Wnt↓, β-catenin/ZEB1↓, cMyc↓, MMP7↓, MALAT1↓, TCF↓, ALDH↓, CD44↓, Shh↓, IL6↓, VEGF↓, eff↑, HK2↓, ROS↑, MMP↓,
4667- RES,  CUR,  SFN,    Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models
- Review, Var, NA
CSCs↓, ChemoSen↑, RadioS↑, ALDH↓, CD44↓, Wnt↓, β-catenin/ZEB1↓, NOTCH↓, HH↓, NF-kB↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GPx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 1,   ROS↝, 1,   mt-ROS↑, 1,   TAC?, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 2,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 2,   lactateProd↓, 1,   SIRT1↓, 1,   SIRT2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   DR4↑, 1,   DR5↑, 1,   MDM2↓, 1,   p27↑, 2,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 1,   TP53↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   ALDH1A1↓, 2,   CD133↓, 3,   CD44↓, 3,   CSCs↓, 5,   EMT↓, 3,   Gli1↓, 2,   GSK‐3β↝, 1,   p‑GSK‐3β↓, 1,   HH↓, 2,   IGF-1R↓, 1,   mTOR↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 3,   NOTCH⇅, 1,   NOTCH2↓, 1,   OCT4↓, 2,   PI3K↓, 3,   PTCH1↓, 1,   PTEN↑, 2,   Shh↓, 2,   Smo↓, 2,   STAT3↓, 2,   STAT5↓, 1,   TCF↓, 1,   TOP2↓, 1,   Wnt↓, 7,  

Migration ⓘ

E-cadherin↑, 3,   GLI2↓, 1,   MALAT1↓, 1,   MMP7↓, 2,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   Snail↓, 1,   SOX4↓, 1,   TET1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   Vim↓, 1,   β-catenin/ZEB1↓, 9,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   IL6↓, 1,   JAK↓, 1,   NF-kB↓, 4,  

Drug Metabolism & Resistance ⓘ

BioEnh?, 1,   ChemoSen↑, 2,   ChemoSen⇅, 1,   eff↑, 3,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   NKG2D↑, 1,  
Total Targets: 104

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ROS↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Migration ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 1,   Dose↝, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 2,   toxicity↓, 1,  
Total Targets: 16

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
9 Resveratrol
1 Pterostilbene
1 Curcumin
1 Sulforaphane (mainly Broccoli)
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#:141  Target#:342  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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