Curcumin / β-catenin/ZEB1 Cancer Research Results

CUR, Curcumin: Click to Expand ⟱
Features:
Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells.
- GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown
-may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
curcumin can act as a pro-oxidant when blue light is applied
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- 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 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of survival and inflammatory transcription NF-κB is a primary, repeatedly validated curcumin target explaining pleiotropic downstream effects
2 STAT3 signaling ↓ STAT3 phosphorylation / activity ↔ or mild suppression Driver Loss of pro-survival and proliferative signaling STAT3 inhibition contributes to growth arrest, apoptosis sensitization, and reduced cytokine signaling in tumors
3 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Curcumin can act as a pro-oxidant in cancer cells with high basal stress while acting antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and caspase activation occur downstream of NF-κB/STAT3 and ROS effects
5 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ or adaptive suppression Secondary Reduced growth and anabolic signaling AKT/mTOR inhibition contributes to growth suppression and autophagy induction in cancer cells
6 Autophagy ↑ autophagy (protective or pro-death) ↑ adaptive autophagy Secondary Stress adaptation vs cell death Autophagy may be cytoprotective or cooperate with apoptosis depending on context and dose
7 HIF-1α / VEGF hypoxia–angiogenesis axis ↓ HIF-1α; ↓ VEGF ↔ minimal effect Secondary Anti-angiogenic pressure Suppression of hypoxia-driven transcription limits angiogenesis and tumor adaptation
8 Cell cycle regulation ↑ G2/M or G1 arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling and epigenetic effects rather than direct CDK inhibition
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT markers and protease activity limit invasive behavior
10 Epigenetic regulation (p300/CBP HAT activity) ↓ histone acetylation ↔ modest Secondary Transcriptional reprogramming Curcumin modulates chromatin via HAT inhibition rather than classic HDAC inhibition


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⟱
3861- CUR,    Curcumin as a novel therapeutic candidate for cancer: can this natural compound revolutionize cancer treatment?
- Review, Var, NA
*antiOx↑, *Inflam↓, PI3K↓, Akt↓, mTOR↓, Wnt↓, β-catenin/ZEB1↓, NF-kB↓, HH↓, NOTCH↓, JAK↓, STAT3↓, ADAM10↓,
4709- CUR,    Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways
- Review, Var, NA
miR-21↓, TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, miR-99↑, JAK↓, STAT↓, cycD1/CCND1↓, P21↑, ChemoSen↑, miR-192-5p↑, cMyc↓, Wnt↓, β-catenin/ZEB1↓, miR-130a↓,
4671- CUR,    Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy
- in-vitro, CRC, NA
CSCs↓, TumCG↓, ChemoSen↑, Wnt↓, β-catenin/ZEB1↓, Shh↓, NOTCH↓, DNMT1↓, STAT3↓, NF-kB↓, EGFR↓, IGFR↓, TumCCA↓, cl‑PARP↑, BAX↑, ECM/TCF↓,
2974- CUR,    Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT15 - in-vitro, CRC, COLO205 - in-vitro, CRC, SW-620 - in-vivo, NA, NA
TumCMig↓, TumCI↓, TumCG↓, TumMeta↓, Sp1/3/4↓, HDAC4↓, FAK↓, CD24↓, E-cadherin↑, EMT↓, TumCP↓, NF-kB↓, AP-1↝, STAT3↓, P53?, β-catenin/ZEB1↓, NOTCH1↝, Hif1a↝, PPARα↝, Rho↓, MMP2↓, MMP9↓,
455- CUR,    Curcumin Affects Gastric Cancer Cell Migration, Invasion and Cytoskeletal Remodeling Through Gli1-β-Catenin
- in-vitro, GC, SGC-7901
Shh↓, Gli1↓, FOXM1↓, β-catenin/ZEB1↓, TumCMig↓, Apoptosis↑, TumCCA↑, Wnt↓, EMT↓, E-cadherin↑, Vim↓,
443- CUR,    Reduced Caudal Type Homeobox 2 (CDX2) Promoter Methylation Is Associated with Curcumin’s Suppressive Effects on Epithelial-Mesenchymal Transition in Colorectal Cancer Cells
- in-vitro, CRC, SW480
DNMT1↓, DNMT3A↓, N-cadherin↓, Vim↓, Wnt↓, Snail↓, Twist↓, β-catenin/ZEB1↓, E-cadherin↑, EMT↓, CDX2↓,
442- CUR,  5-FU,    Curcumin may reverse 5-fluorouracil resistance on colonic cancer cells by regulating TET1-NKD-Wnt signal pathway to inhibit the EMT progress
- in-vitro, CRC, HCT116
Apoptosis↑, TumCP↓, TumCCA↑, TET1↑, NKD2↑, Wnt↓, EMT↓, Vim↑, E-cadherin↓, β-catenin/ZEB1↓, TCF↓, AXIN1↓,
449- CUR,    Curcumin Suppresses the Colon Cancer Proliferation by Inhibiting Wnt/β-Catenin Pathways via miR-130a
- vitro+vivo, CRC, SW480
TumCP↓, β-catenin/ZEB1↓, TCF↓, miR-21↓, NKD2↑, miR-130a↓,
152- CUR,    Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer
- in-vivo, Pca, NA
β-catenin/ZEB1↓, AR↓, STAT3↓, p‑Akt↓, Mcl-1↓, Bcl-xL↓, cl‑PARP↑, miR-21↓, miR-205↑, TumCG↓, TumCP↓, TumCI↓, angioG↓, TumMeta↓,
12- CUR,    Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells
- in-vitro, MB, DAOY
HH↓, Shh↓, Gli1↓, PTCH1↓, cMyc↓, n-MYC↓, cycD1/CCND1↓, Bcl-2↓, NF-kB↓, Akt↓, β-catenin/ZEB1↓, survivin↓, Apoptosis↑, ChemoSen↑, RadioS↑, eff↑,
15- CUR,  UA,    Effects of curcumin and ursolic acid in prostate cancer: A systematic review
- Review, Pca, NA
NF-kB↝, Akt↝, AR↝, Apoptosis↝, Bcl-2↝, Casp3↝, BAX↝, P21↝, ROS↝, Bcl-xL↝, JNK↝, MMP2↝, P53↝, PSA↝, VEGF↝, COX2↝, cycD1/CCND1↝, EGFR↝, IL6↝, β-catenin/ZEB1↝, mTOR↝, NRF2↝, AP-1↝, Cyt‑c↝, PI3K↝, PTEN↝, Cyc↝, TNF-α↝,
126- CUR,    Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vitro, Pca, DU145
miR-34a↑, β-catenin/ZEB1↓, cMyc↓, P21↑, cycD1/CCND1↓, PCNA↓, TumCG↓,
420- CUR,    Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Vim↓, Fibronectin↓, β-catenin/ZEB1↓, E-cadherin↓, CD44↑, CD24↓, OCT4↓, Nanog↓, SOX2↓,
424- CUR,    Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Src↓, p‑STAT1↓, p‑Akt↓, p‑p44↓, p‑p42↓, RAS↓, Raf↓, Vim↓, β-catenin/ZEB1↓, P53↓, Bcl-2↓, Mcl-1↓, PIAS-3↑, SOCS-3↑, SOCS1↑, ROS↑, NF-kB↓, PAO↑, SSAT↑, P21↑, Bak↑,
165- CUR,    Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓, β-catenin/ZEB1↓, p‑Akt↓, GSK‐3β↓, p‑β-catenin/ZEB1↑, cycD1/CCND1↓, cMyc↓, chemoPv↑, TumCP↓,
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 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↝, 1,   PAO↑, 1,   ROS↑, 1,   ROS↝, 1,  

Mitochondria & Bioenergetics ⓘ

p‑p42↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 4,   PPARα↝, 1,   SSAT↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↝, 1,   p‑Akt↓, 3,   Apoptosis↑, 4,   Apoptosis↝, 1,   Bak↑, 1,   BAX↑, 1,   BAX↝, 1,   Bcl-2↓, 2,   Bcl-2↝, 1,   Bcl-xL↓, 1,   Bcl-xL↝, 1,   Casp3↝, 1,   Cyt‑c↝, 1,   JNK↝, 1,   Mcl-1↓, 2,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

miR-192-5p↑, 1,   miR-205↑, 1,   miR-21↓, 3,  

DNA Damage & Repair ⓘ

DNMT1↓, 2,   DNMT3A↓, 1,   P53?, 1,   P53↓, 1,   P53↝, 1,   cl‑PARP↑, 2,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

Cyc↝, 1,   cycD1/CCND1↓, 4,   cycD1/CCND1↝, 1,   P21↑, 3,   P21↝, 1,   TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   AXIN1↓, 1,   CD24↓, 2,   CD44↓, 1,   CD44↑, 1,   CDX2↓, 1,   CSCs↓, 2,   EMT↓, 4,   FOXM1↓, 1,   Gli1↓, 2,   GSK‐3β↓, 1,   HDAC4↓, 1,   HH↓, 3,   IGFR↓, 1,   miR-34a↑, 1,   miR-99↑, 1,   mTOR↓, 1,   mTOR↝, 1,   n-MYC↓, 1,   Nanog↓, 1,   NKD2↑, 2,   NOTCH↓, 3,   NOTCH1↝, 1,   OCT4↓, 1,   PI3K↓, 1,   PI3K↝, 1,   PIAS-3↑, 1,   PTCH1↓, 1,   PTEN↝, 1,   RAS↓, 1,   Shh↓, 3,   SOX2↓, 1,   Src↓, 1,   STAT↓, 1,   p‑STAT1↓, 1,   STAT3↓, 4,   TCF↓, 2,   TumCG↓, 4,   Wnt↓, 7,  

Migration ⓘ

AP-1↝, 2,   E-cadherin↓, 2,   E-cadherin↑, 3,   FAK↓, 1,   Fibronectin↓, 1,   miR-130a↓, 2,   MMP2↓, 1,   MMP2↝, 1,   MMP9↓, 1,   N-cadherin↓, 1,   p‑p44↓, 1,   Rho↓, 1,   Snail↓, 1,   TET1↑, 1,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 6,   TumMeta↓, 2,   Twist↓, 1,   Vim↓, 4,   Vim↑, 1,   β-catenin/ZEB1↓, 15,   β-catenin/ZEB1↝, 1,   p‑β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ECM/TCF↓, 1,   EGFR↓, 1,   EGFR↝, 1,   Hif1a↝, 1,   VEGF↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↝, 1,   IL6↝, 1,   JAK↓, 2,   NF-kB↓, 6,   NF-kB↝, 1,   PSA↝, 1,   SOCS-3↑, 1,   SOCS1↑, 1,   TNF-α↝, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   AR↝, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 4,   eff↑, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 2,   AR↝, 1,   EGFR↓, 1,   EGFR↝, 1,   FOXM1↓, 1,   IL6↝, 1,   PSA↝, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 136

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
16 Curcumin
1 5-fluorouracil
1 Ursolic acid
1 Resveratrol
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#:65  Target#:342  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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