Curcumin / Wnt Cancer Research Results

CUR, Curcumin: Click to Expand ⟱
Features:
Curcumin is the main active ingredient in Turmeric. 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).

Curcumin — Curcumin is a turmeric-derived polyphenolic curcuminoid and diarylheptanoid from Curcuma longa, functionally best classified as a natural-product small molecule / nutraceutical candidate with pleiotropic redox, inflammatory, transcriptional, metabolic, and chemosensitizing activity. The standard abbreviation is CUR. It is the principal active pigment of turmeric rhizome, usually studied as purified curcumin, curcuminoid mixtures, turmeric extract, phytosomal curcumin, liposomal curcumin, nanoparticle curcumin, or piperine-enhanced formulations. Its oncology relevance is mechanistically broad but clinically constrained by poor aqueous solubility, rapid metabolism, low free systemic exposure, formulation variability, and insufficient well-powered cancer outcome trials.

Primary mechanisms (ranked):

  1. Suppression of NF-κB / STAT3 inflammatory-survival signaling, reducing cytokine, COX-2, iNOS, anti-apoptotic, invasion, and treatment-resistance programs.
  2. Biphasic redox modulation: ROS buffering in normal/inflamed tissue but ROS↑, GSH depletion, thioredoxin reductase disruption, and oxidative stress amplification in susceptible cancer models at sufficient exposure.
  3. Mitochondrial injury and intrinsic apoptosis, including mitochondrial membrane potential loss, cytochrome-c release, caspase activation, PARP cleavage, and ER-stress/UPR involvement.
  4. PI3K/AKT/mTOR and MAPK pathway modulation, contributing to growth arrest, autophagy modulation, apoptosis sensitization, and reduced survival signaling.
  5. Wnt/β-catenin, Hedgehog/GLI, Notch, and cancer-stem-cell suppression, reducing stemness, EMT, invasion, and recurrence-associated phenotypes in models.
  6. Hypoxia / HIF-1α and glycolysis inhibition, including reduced GLUT1, HK2, LDHA, PKM2, lactate/ECAR, and Warburg-like metabolic support in selected models.
  7. Anti-angiogenic and anti-metastatic modulation, including VEGF, MMPs, uPA, CXCR4/SDF-1, TGF-β/α-SMA, FAK, and EMT-related axes.
  8. Epigenetic and transcriptional reprogramming, including reported HDAC, DNMT, EZH2, Sp-family, p53, and microRNA-related effects.
  9. NRF2 modulation: generally cytoprotective in normal cells but potentially protective for cancer cells when NRF2 is activated; NRF2 suppression/knockdown can increase curcumin-induced ROS stress in some tumor models.
  10. Chemosensitization and radiosensitization, with parallel normal-tissue protective signals reported in some mucositis, dermatitis, oxidative-stress, and radioprotection contexts.

Bioavailability / PK relevance: Conventional oral curcumin has poor systemic bioavailability because of low solubility, low absorption, rapid conjugation, and rapid elimination. Oral trials have used doses up to gram-level daily dosing, but circulating free curcumin is typically low; measured plasma exposure often reflects conjugated curcumin. Piperine, phospholipid/phytosome, micellar, liposomal, nanoparticle, and other enhanced formulations can raise exposure, but each formulation should be treated as a distinct translational entity. Delivery constraints are central for oncology interpretation.

In-vitro vs systemic exposure relevance: Common in-vitro anticancer concentrations, often in the low-to-mid micromolar range and sometimes higher, frequently exceed achievable free plasma exposure from standard oral curcumin. Therefore, direct systemic anticancer claims from cell culture should be weighted cautiously unless supported by tissue-local exposure, enhanced formulation data, local delivery, IV/liposomal delivery, or clinically measured pharmacodynamic biomarkers.

Clinical evidence status: Preclinical evidence is extensive; human oncology evidence is mainly small human, biomarker, pilot, chemoprevention, adjunctive, symptom-management, and formulation trials. Current authoritative oncology summaries judge evidence inadequate to recommend curcumin-containing products as cancer treatment or as routine adjunct anticancer therapy, although symptom-support areas such as oral mucositis, radiation dermatitis, oxidative-status measures, and quality of life have more suggestive but still confirmatory-level evidence.


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

Curcumin Cancer Mechanism Ranking

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 NF-κB / STAT3 inflammatory survival signaling NF-κB ↓; STAT3 ↓; IL-6/TNF-α/COX-2/iNOS ↓; Bcl-2/Bcl-xL/survivin programs ↓ Inflammatory tone ↓; tissue-protective anti-inflammatory effect likely context-dependent R/G Reduced survival, inflammation, invasion, and therapy-resistance signaling Most central and industry-relevant axis; explains many downstream effects but is not curcumin-specific.
2 Biphasic redox stress and antioxidant buffering ROS ↑ (dose-dependent); GSH ↓; antioxidant reserve ↓; oxidative apoptosis ↑ ROS ↓; NRF2/SOD/GSH/catalase/HO-1 often ↑ in stress models R/G Selective redox pressure in susceptible tumor cells with normal-cell protection in lower-stress settings Direction depends strongly on concentration, formulation, light exposure, basal redox state, and tumor antioxidant capacity.
3 Thioredoxin reductase and GSH linked redox systems TrxR inhibition or redox cycling ↑; GSH depletion ↑; oxidative stress ↑ Usually buffered or antioxidant response ↑ at non-toxic exposure R/G Collapse of tumor redox compensation Mechanistically important for ROS amplification and radiosensitization; achievable exposure remains a major constraint.
4 Mitochondrial depolarization and intrinsic apoptosis ΔΨm ↓; cytochrome-c ↑; caspase-3/9 ↑; PARP cleavage ↑; apoptosis ↑ Generally ↔ or protected under oxidative/inflammatory stress R/G Execution of apoptosis after upstream redox and survival-signal disruption Central cytotoxic endpoint in many cell models; often downstream of ROS, ER stress, AKT/mTOR suppression, or p53 modulation.
5 PI3K / AKT / mTOR and autophagy balance PI3K ↓; AKT ↓; mTOR ↓; survival signaling ↓; autophagy ↑ or mixed Stress-adaptive autophagy ↔ or ↑ (context-dependent) R/G Growth suppression and apoptosis sensitization Autophagy may be cytotoxic or protective depending on model and timing; combination logic may require autophagy-state interpretation.
6 Wnt / β-catenin / Hedgehog / Notch stemness signaling β-catenin ↓; GLI/Hedgehog ↓; Notch ↓; CD133/CD44/OCT4/SOX2-like stemness markers ↓ Generally ↔; possible normal stem-cell effects are tissue/context-dependent G Reduced cancer stemness, EMT, self-renewal, and recurrence-associated phenotypes Important for anti-metastatic and anti-CSC positioning; evidence is mainly preclinical.
7 HIF-1α / glycolysis / Warburg metabolism HIF-1α ↓; GLUT1 ↓; HK2 ↓; LDHA ↓; PKM2 ↓; lactate/ECAR ↓; ATP stress ↑ Metabolic effects ↔ or adaptive; normal-cell toxicity depends on exposure G Reduced hypoxic adaptation and glycolytic energy support Mechanistically relevant but formulation and tissue exposure are critical; hypoxic tumors may be more relevant than normoxic cell culture.
8 EMT / invasion / metastasis matrix axis EMT ↓; MMP2/MMP9 ↓; uPA ↓; FAK ↓; CXCR4/SDF-1 ↓; migration/invasion ↓ Inflammation-linked remodeling ↓; wound-healing effects context-dependent G Anti-invasive and anti-metastatic phenotype Strongly supported in models; clinical anti-metastatic efficacy is not established.
9 VEGF / angiogenesis / hypoxia interface VEGF ↓; HIF-1α ↓; angiogenic signaling ↓ Angiogenesis modulation ↔ or ↓ (context-dependent) G Reduced tumor vascular-support signaling Overlaps with NF-κB, HIF-1α, STAT3, and inflammatory cytokine suppression.
10 Epigenetic and transcriptional reprogramming HDAC ↓; DNMT1/3A ↓; EZH2 ↓; Sp proteins ↓; p53 ↑ or restored in selected models Broad transcriptional effects possible; selectivity uncertain G Reactivation of growth-control and differentiation-associated programs Biologically plausible but highly model-dependent; direct target specificity is lower than pathway-level interpretation.
11 Ferroptosis and iron redox stress Iron/redox stress ↑; lipid peroxidation ↑; GPX4/GSH axis may ↓ (model-dependent) Iron-chelation and antioxidant protection may occur (context-dependent) R/G Potential ferroptosis contribution in susceptible tumor models Curcumin can behave as an iron chelator, antioxidant, or pro-oxidant depending on exposure, formulation, and cancer redox context.
12 NRF2 cytoprotection risk NRF2 ↑ may protect tumor cells; NRF2 depletion can enhance curcumin-induced ROS stress in some models NRF2 ↑ supports antioxidant and anti-inflammatory tissue protection G Dual-edged stress-response modulation Important caution for antioxidant matrix use: NRF2 activation is favorable in normal-cell protection but may be undesirable in NRF2-addicted tumors.
13 Chemosensitization and radiosensitization Chemo response ↑; radiation response ↑; apoptosis ↑; resistance pathways ↓ Chemo/radiation injury may ↓ in mucositis, dermatitis, and oxidative-stress contexts R/G Adjunct sensitization with possible normal-tissue protection Attractive translational axis, but clinical evidence remains mainly pilot/small-study; interaction risk should be checked per regimen.
14 Clinical Translation Constraint Free systemic exposure often insufficient for direct cytotoxic extrapolation from in-vitro micromolar data Enhanced formulations may improve exposure but may also alter safety, liver-risk profile, and interaction potential G Bioavailability and formulation dominate translational interpretation Separate ordinary curcumin, turmeric extract, piperine-enhanced, phytosomal, micellar, liposomal, nanoparticle, and IV/liposomal products where possible.

TSF legend:

P: 0–30 min

R: 30 min–3 hr

G: >3 hr
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⟱
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↓,

6229- CUR,    Wntb-catenin_pathways_in_cervical_cancer_cells">Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells
- in-vitro, Cerv, NA
TumCI↓, curcumin inhibits invasion and proliferation of cervical cancer cells via impairment of NF-kB and Wnt/β-catenin pathways,
TumCP↓,
NF-kB↓,
Wnt↓,
β-catenin/ZEB1↓,

6227- CUR,    Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations
- Review, Var, NA
Wnt↓, By targeting multiple molecular pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, JAK/STAT3, MAPK, NF-κB, and Notch, curcumin suppresses cancer growth and induces apoptosis.
β-catenin/ZEB1↓,
PI3K↓,
Akt↓,
mTOR↓,
JAK↓,
STAT3↓,
MAPK↓,
NF-kB↓,
NOTCH↓,
TumCG↓,
Apoptosis↑,
GSK‐3β↓, curcumin directly targets β-catenin and key Wnt/β-catenin regulators, including Dvl-2, Dvl-3, and GSK-3β.
cMyc↓, curcumin downregulates downstream oncogenic effectors such as c-Myc and Survivin while upregulating Axin-2, thereby inducing G2/M cell cycle arrest and apoptosis.
survivin↓,
Axin2↑,
TumCCA↑,
PTEN↑, curcumin upregulates PTEN expression, restoring its negative regulatory effect on the PI3K/Akt pathway.
P53↑, Curcumin’s activation and stabilization of p53 have been demonstrated in multiple cancer cell lines
ROS↑, In cervical cancer cells, curcumin induced apoptosis and ROS accumulation. Curcumin treatment elevated cleaved caspase-3 and PARP levels, markers of apoptosis.
Casp3↑,
PARP↑,
Ferroptosis↑, Ferroptosis Induction by Curcumin
angioG↓, Curcumin Inhibits Angiogenesis, Invasion, and Metastasis in Cancer Cells
TumCI↓,
TumMeta↓,
BioAv↓, curcumin’s clinical translation is limited by its poor bioavailability, rapid metabolism, and low systemic stability.
Half-Life↓,
ChemoSen↑, Synergistic Effects of Curcumin with Chemotherapy and Nanoparticle-Based Drug Delivery Systems

6223- CUR,    Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects
- Review, Var, NA
Ferroptosis↑, including the induction of ferroptosis by regulating the SLC7A11/GPX4 axis
GutMicro↑, and modulating gut microbiota metabolism. I
Akt↓, it inhibits pro-tumorigenic signals such as Akt/mTOR, NF-κB, Wnt/β-catenin, and STAT3, thereby blocking tumor proliferation, invasion, and metastasis
mTOR↓,
NF-kB↓,
Wnt↓,
β-catenin/ZEB1↓,
STAT3↓,
TumCP↓,
TumCI↓,
TumMeta↓,
AMPK↑, activates tumor-suppressive and cytoprotective pathways, including AMPK, p53, and nuclear factor erythroid 2-related factor 2 (Nrf2), which induce cell cycle arrest and apoptosis
P53↑,
NRF2↑,
TumCCA↑,
Apoptosis↑,
Casp↑, activation of the Caspase cascade
GPx4↓, as well as ferroptosis by inhibiting the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis [5]
DNMTs↓, inhibiting epigenetic regulatory mechanisms such as DNMTs and HDACs.
HDAC↓,
VEGF↓, inhibiting VEGF signaling and enhances the immune microenvironment by improving T cell and NK cell function
Imm↑,
NK cell↑,
Warburg↓, Curcumin effectively reverses the Warburg effect and interferes with glucose metabolism by targeting HIF-1α and inhibiting key enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
Hif1a↓,
HK2↓,
PKM2↓,
LDHA↓,
GLUT1↓, as well as the functions of glucose transporter 1 (GLUT1) and monocarboxylate transporters (MCTs) [12].
MCT1↓,
AMPK↑, curcumin activates signaling pathways such as AMPK, downregulates fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1),
FASN↓,
SCD1↓,
GLS↓, Curcumin extensively intervenes in amino acid metabolism by inhibiting the activity of glutaminase (GLS), ornithine decarboxylase (ODC), and other enzymes,
Apoptosis↑, inducing apoptosis through mechanisms such as disrupting the electron transport chain, reducing membrane potential, and promoting the generation of reactive oxygen species (ROS)
ETC↓,
MMP↓,
ROS↑,
lipid-P↑, curcumin induces lipid peroxidation and collapses redox homeostasis, thereby activating the ferroptosis program [
ChemoSen↑, blocking invasion and metastasis, and enhancing chemosensitivity.
PDK1↓, In hypoxic pancreatic cancer cells, curcumin downregulates the expression of GLUT1, HK2, LDHA, and PDK1 by inhibiting the Beclin1/HIF-1α axis, which results in reduced ATP production and inhibited cell proliferation [
Beclin-1↓,
ATP↓,
Glycolysis↓, inhibiting glycolysis
GlucoseCon↓, decreased glucose uptake and increased lactate production
lactateProd↑,
MMPs↓, reduces MMP, GSH, and G6PD activities
GSH↓, inhibition of SLC7A11 to limit GSH synthesis, thereby triggering the collapse of the antioxidant defense system
G6PD↓,
OXPHOS↓, downregulate OXPHOS and glycolysis activities
SREBP2↓, curcumin treatment leads to a marked downregulation of the mRNA expression of SREBP and its target genes. inhibiting the expression of NPC1L1, SREBP-2, and HNF1α
COX2↓, curcumin exerts anti-tumor effects by downregulating the expression of NF-κB, COX-2, and AP-1
AP-1↓,
NADH↓, decreased GPx4 and FSP1 expression, induced ferroptosis by inhibiting GSH-GPx4 and FSP1-CoQ 10-NADH pathways
NRF2↑, it inhibits GPX4 and activates Nrf2 and heme oxygenase-1 (HO-1). This results in an abnormal accumulation of intracellular Fe2+, ROS, lipid peroxides, and malondialdehyde (MDA), along with a depletion of GSH
HO-1↑,
Iron↑,
MDA↑,
*ROS↓, studies have demonstrated that the topical application of curcumin on the skin exerts antitumor effects by synergistically downregulating COX-2 and ODC activities, alleviating oxidative damage, and concurrently inhibiting inflammatory proliferation i
*Inflam↓,

6217- CUR,    Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway
- Review, Var, NA
Wnt↓, Curcumin administration participates to the downregulation of the WNT/β-catenin pathway and thus, through this action, in tumor growth control.
β-catenin/ZEB1↓,
PPARγ↑, Curcumin stimulates PPARγ
Akt↓, Curcumin inhibits Akt pathway
*ROS↓, (1) Curcumin reduces oxidative
*Inflam↓, (2) Curcumin reduces chronic inflammation
Bcl-2↓, (4) Curcumin downregulates WNT pathway and its target genes, inhibits Bcl-2 and activates GSK-3beta;
GSK‐3β↑,
NF-kB↓, (5) Curcumin inhibits NF-ϰB and COX-2
COX2↓,

6215- CUR,    Curcumin: biochemistry, pharmacology, advanced drug delivery systems, and its epigenetic role in combating cancer
- Review, Var, NA
*antiOx↑, Curcumin exerts potent antioxidant, anti-inflammatory, and anticancer effects by modulating multiple signaling pathways, including NF-κB, PI3K/Akt, and Wnt/β-catenin.
*Inflam↓,
*BioAv↓, curcumin’s clinical application is limited by poor solubility, rapid metabolism, and low systemic bioavailability.
NF-kB↓, graphical abstract
PI3K↓,
Akt↓,
Wnt↓,
β-catenin/ZEB1↓,
DNMTs↓,
TumCI↓,
TumMeta↓,
*BioAv↑, Advanced drug delivery systems such as nanoparticles, liposomes, and micelles have been developed to address these challenges. These systems enhance curcumin’s solubility, stability, and targeted delivery, improving therapeutic efficacy while minimiz
*BioAv↑, coadministration with piperine, lipid-based formulations, and nanoparticle microencapsulation have been developed. Piperine has been shown to increase curcumin absorption by up to 2000 percent
angioG↓, Curcumin is also known for its antiangiogenic action through its inhibitory activity against vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)
VEGF↓,
MMPs↓,
*ROS↓, suppresses oxidative stress by scavenging free radicals and enhancing the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase
*SOD↑,
*Catalase↑,
*GSTs↑, timulating phase II detoxifying enzymes such as glutathione S-transferase (GST), UDP-glucuronosyltransferase, and heme oxygenase-1 (HO-1).
*HO-1↑,
*NRF2↑, It also enhances the activity of the transcription factor Nrf2, which regulates genes crucial for cellular redox homeostasis and safeguarding cells against oxidative damage
mTOR↓, 0 to 50 μM, treatment was associated with decreased phosphorylation of Akt kinase (Akt), mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK3β), Forkhead box protein O1 (FOXO1), and other proteins
GSK‐3β↓,
FOXO1↓,
*radioP↑, Reduced radiation-induced dermatitis and inflammatory cytokine expression (IL-1, IL-6, TNF-α)
*IL1↓,
*IL6↓,
*TNF-α↓,
HATs↓, curcumin has been described as an agent that reduces histone acetylation by inhibiting HAT (histone acetyltransferases), such as the p300/CBP family of proteins
HDAC↓, curcumin has been detected to be an HDI and has the ability to inhibit the expressions of HDACs, like HDAC1, HDAC3, and HDAC8,
ROS↑, Elevating the levels of reactive oxygen species (ROS) in colon adenocarcinoma cells is one of the outcomes of treatment with curcumin, which results in a decline in cell proliferation and viability
ROS↑, at higher concentrations or in the presence of transition metal ions (e.g. Cu2+, Fe2+/Fe3+), curcumin can paradoxically act as a pro-oxidant.
MMP↓, Excess ROS damages mitochondrial membranes, oxidizes nucleic acids, lipids, and proteins, and activates apoptotic cascades via cytochrome c release and caspase activation
Casp↑,
Cyt‑c↑,
COX1↓, curcumin acts as a partial and condition-dependent inhibitor of both COX-1 and COX-2.
COX2↓,
PGE2↓, At lower or therapeutic concentrations, curcumin predominantly downregulates COX-2 and reduces prostaglandin E2 (PGE2) synthesis.
*cytoP450↓, curcumin’s capacity to inhibit cytochrome P450 enzymes may influence the metabolism of numerous medicines over extended durations.
ChemoSen↑, curcumin has been integrated with standard chemotherapy agents, including doxorubicin, cisplatin, and paclitaxel, to enhance cancer treatment efficacy
cardioP↑, co-delivery of curcumin and doxorubicin via nanoparticles improved anticancer effectiveness and decreased cardiotoxicity.
eff↑, concurrent treatment of curcumin and resveratrol has demonstrated increased anti-inflammatory and anticancer properties

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.

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↓,


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 ⓘ

ATF3↑, 1,   Ferroptosis↑, 2,   GPx4↓, 1,   GSH↓, 1,   HO-1↑, 2,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NADH↓, 1,   NRF2↑, 2,   OXPHOS↓, 1,   ROS↑, 4,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   ETC↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   cMyc↓, 2,   FASN↓, 1,   G6PD↓, 1,   GLS↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↑, 1,   LDHA↓, 1,   PDK1↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM2↓, 1,   PPARγ↑, 2,   SCD1↓, 2,   SREBP2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 6,   Apoptosis↑, 8,   BAX↑, 1,   Bcl-2↓, 1,   Casp↑, 2,   Casp3↑, 1,   Cyt‑c↑, 1,   Ferroptosis↑, 2,   MAPK↓, 2,   MCT1↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

miR-25-5p↓, 1,  

Transcription & Epigenetics ⓘ

HATs↓, 1,   miR-192-5p↑, 1,   miR-21↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 2,   DNMT3A↓, 1,   DNMTs↓, 2,   P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   AXIN1↓, 1,   Axin2↑, 1,   CD44↓, 1,   CDX2↓, 1,   CSCs↓, 2,   EMT↓, 3,   FOXM1↓, 1,   FOXO1↓, 1,   Gli1↓, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   HDAC↓, 2,   HH↓, 2,   HH↝, 1,   IGFR↓, 1,   miR-330-5p↑, 1,   miR-99↑, 1,   mTOR↓, 5,   NKD2↑, 1,   NOTCH↓, 4,   NOTCH↝, 1,   PI3K↓, 3,   PTEN↑, 3,   Shh↓, 2,   STAT↓, 1,   STAT3↓, 4,   TCF↓, 1,   TumCG↓, 2,   Wnt↓, 15,   Wnt↝, 1,  

Migration ⓘ

AP-1↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↝, 1,   miR-130a↓, 1,   MMPs↓, 2,   N-cadherin↓, 1,   Snail↓, 1,   TET1↑, 1,   TGF-β↓, 2,   TumCI↓, 5,   TumCMig↓, 2,   TumCP↓, 4,   TumMeta↓, 3,   Twist↓, 1,   Vim↓, 2,   Vim↑, 1,   β-catenin/ZEB1↓, 12,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ECM/TCF↓, 1,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 3,   IL1↓, 1,   IL6↓, 1,   IL8↓, 1,   Imm↑, 1,   JAK↓, 3,   NF-kB↓, 10,   NK cell↑, 1,   PGE2↓, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 6,   eff↑, 1,   Half-Life↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   FOXM1↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,  
Total Targets: 134

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSTs↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

cytoP450↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1↓, 1,   IL6↓, 1,   Inflam↓, 4,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

radioP↑, 1,  
Total Targets: 17

Scientific Paper Hit Count for: Wnt, Wingless-related integration site
16 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

 

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