Database Query Results : Curcumin, , Wnt

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


Wnt, Wingless-related integration site: Click to Expand ⟱
Source:
Type:
The Wnt signaling pathway is a complex network of proteins that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and migration. It is particularly important during embryonic development and tissue homeostasis. Dysregulation of the Wnt pathway has been implicated in various cancers, making it a significant area of research in oncology.
Wnt Ligands
Wnt1: Often overexpressed in breast cancer and some types of leukemia.
Wnt Receptors
Frizzled (Fzd) Receptors: Different Fzd receptors (e.g., Fzd1, Fzd2, Fzd7) have been implicated in various cancers:
Fzd1: Overexpressed in colorectal cancer.
Fzd2: Associated with breast cancer and prostate cancer.
Fzd7: Linked to gastric cancer and glioblastoma.
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↑, fig 1
*Inflam↓,
PI3K↓, By inhibiting pro-survival and pro-inflammatory signaling cascades such as PI3K/Akt/mTOR, MAPK, Wnt/β-catenin, NF-κB, Hedgehog, Notch, and JAK/STAT3, curcumin effectively impedes cancer cell growth and promotes apoptosis.
Akt↓,
mTOR↓,
Wnt↓,
β-catenin/ZEB1↓,
NF-kB↓,
HH↓,
NOTCH↓,
JAK↓,
STAT3↓,
ADAM10↓, Curcumin may inhibit the function of the Notch pathway in cancer by inhibiting Notch pathway activators such as gamma secretases, Notch ligands, or ADAM10.

4709- CUR,    Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways
- Review, Var, NA
miR-21↓, Curcumin can effectively repress the miR-21/PTEN/Akt molecular pathway to inhibit cell proliferation and induce apoptosis in gastric cancer cells
TumCP↓, Curcumin can inhibit the proliferation, migration, invasion and promote apoptosis of retinoblastoma cells, which function through up-regulating the miR-99a expression and then inhibiting JAK/STAT signaling pathway
TumCMig↓,
TumCI↓,
Apoptosis↑,
miR-99↑,
JAK↓,
STAT↓,
cycD1/CCND1↓, curcumin can suppress the cell proliferation by down-regulations of cyclinD1 and up-regulations of p21 expression.
P21↑,
ChemoSen↑, curcumin combined with chemotherapy drugs may play a better therapeutic effect via JAK/STAT signaling pathway
miR-192-5p↑, curcumin enhanced the expression level of miR−192−5p and decreased the expression of c−Myc.
cMyc↓,
Wnt↓, curcumin suppresses colon cancer by inhibiting Wnt/β-catenin pathway via down-regulating miR-130a
β-catenin/ZEB1↓,
miR-130a↓,

4650- CUR,    Curcumin and cancer stem cells: curcumin has asymmetrical effects on cancer and normal stem cells
- Review, Var, NA
SCD1↓, Curcumin has been shown to have numerous cytotoxic effects on cancer stem cells (CSCs).
IL6↓, This is due to its suppression of the release of cytokines, particularly interleukin (IL)-6, IL-8 and IL-1
IL8↓,
IL1↓,
*selectivity↑, curcumin has little toxicity against normal stem cells (NSCs).
Wnt↝, effects at multiple sites along CSC pathways, such as Wnt, Notch, Hedgehog and FAK.
NOTCH↝,
HH↝,
FAK↝,

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↓, Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth.
TumCG↓,
ChemoSen↑, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy,
Wnt↓, Three major signaling pathways in which curcumin plays a pivotal role in CSC self-renewal behavior are the Wnt/β-catenin, Sonic Hedgehog (SHH), and Notch pathways
β-catenin/ZEB1↓,
Shh↓,
NOTCH↓,
DNMT1↓, Figure 1
STAT3↓,
NF-kB↓,
EGFR↓,
IGFR↓,
TumCCA↓,
cl‑PARP↑,
BAX↑,
ECM/TCF↓,

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↓, induced S phase cell cycle arrest
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↓, Wnt3a
Snail↓, Snail1
Twist↓,
β-catenin/ZEB1↓,
E-cadherin↑,
EMT↓, Curcumin incubation inhibited EMT
CDX2↓,

436- CUR,    Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti‐lung cancer cell invasion
- in-vitro, Lung, A549
miR-25-5p↓,
miR-330-5p↑,
MAPK↓,
Wnt↓,

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↑, block of G0/G1 phase
TET1↑,
NKD2↑,
Wnt↓,
EMT↓,
Vim↑,
E-cadherin↓,
β-catenin/ZEB1↓,
TCF↓, TCF4
AXIN1↓, Axin

123- CUR,    Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells
- in-vitro, Colon, LoVo - in-vitro, Colon, COLO205 - in-vitro, Pca, PC3 - in-vitro, Pca, 22Rv1
NF-kB↓, curcumin analog
ATF3↑, our study showed that ATF3 was up-regulated by curcumin in both LNCaP and C4-2B cells
HO-1↑, Our data confirmed the tumor-inhibitory effects of HMOX-1 gene in prostate cancer cells, which was up-regulated by curcumin treatment.
Wnt↓, Wnt, PIK3/AKT/mTOR, and NF-κB signaling pathways were primarily inhibited by curcumin treatment
Akt↓,
mTOR↓,
PTEN↑, and PTEN dependent cell cycle arrest and apoptosis pathways were found to be elevated.
Apoptosis↑,
TGF-β↓, TGF-β signaling pathway was inhibited by curcumin treatment in androgen-dependent and independent manners.
PPARγ↑, Curcumin was also shown to induce PPAR-γ gene expression and inhibit hepatic stellate cell (HSC) activation by interrupting TGF-β signaling in vitro

124- CUR,    Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, C4-2B
TGF-β↓, significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR)
Wnt↓,
PI3k/Akt/mTOR↓,
NF-kB↓, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited
PTEN↑,
Apoptosis↑,
TumCCA↑, Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment.

4667- RES,  CUR,  SFN,    Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models
- Review, Var, NA
CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ATF3↑, 1,   HO-1↑, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   PI3k/Akt/mTOR↓, 1,   PPARγ↑, 1,   SCD1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 5,   BAX↑, 1,   MAPK↓, 1,  

Kinase & Signal Transduction ⓘ

miR-25-5p↓, 1,  

Transcription & Epigenetics ⓘ

miR-192-5p↑, 1,   miR-21↓, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 2,   DNMT3A↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   AXIN1↓, 1,   CD44↓, 1,   CDX2↓, 1,   CSCs↓, 2,   EMT↓, 3,   FOXM1↓, 1,   Gli1↓, 1,   HH↓, 2,   HH↝, 1,   IGFR↓, 1,   miR-330-5p↑, 1,   miR-99↑, 1,   mTOR↓, 2,   NKD2↑, 1,   NOTCH↓, 3,   NOTCH↝, 1,   PI3K↓, 1,   PTEN↑, 2,   Shh↓, 2,   STAT↓, 1,   STAT3↓, 2,   TCF↓, 1,   TumCG↓, 1,   Wnt↓, 10,   Wnt↝, 1,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↝, 1,   miR-130a↓, 1,   N-cadherin↓, 1,   Snail↓, 1,   TET1↑, 1,   TGF-β↓, 2,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 2,   Twist↓, 1,   Vim↓, 2,   Vim↑, 1,   β-catenin/ZEB1↓, 7,  

Angiogenesis & Vasculature ⓘ

ECM/TCF↓, 1,   EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1↓, 1,   IL6↓, 1,   IL8↓, 1,   JAK↓, 2,   NF-kB↓, 5,  

Synaptic & Neurotransmission ⓘ

ADAM10↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   FOXM1↓, 1,   IL6↓, 1,  
Total Targets: 74

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

selectivity↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: Wnt, Wingless-related integration site
11 Curcumin
1 5-fluorouracil
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#:377  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page