Curcumin / PI3K 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
PI3K, Phosphatidylinositide-3-Kinases: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-CS
Type:
Phosphatidylinositol 3-kinase (PtdIns3K or PI3K) is a family of enzymes that play a crucial role in cell signaling pathways, particularly in the regulation of cell growth, survival, and metabolism. The PI3K pathway is one of the most frequently altered pathways in human cancer. Inhibition of the PI3K pathway has been explored as a therapeutic strategy for cancer treatment. Several PI3K inhibitors have been developed and are currently being tested in clinical trials. These inhibitors can target specific components of the pathway, such as PI3K, AKT, or mTOR.

Class I phosphoinositide 3-kinase (PI3K)
Class III PtdIns3K
In contrast to the class III PtdIns3K as a positive regulator of autophagy, class I PI3K-AKT signaling has an opposing effect on the initiation of autophagy.

PI3K inhibitors include:
-Idelalisib , Copanlisib, Alpelisib
-LY294002?
-Wortmannin: potent PI3K inhibitor, has some associated toxicity.
-Quercetin:
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
Scientific Papers found: Click to Expand⟱
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

6222- CUR,    Anticancer Molecular Mechanisms of Curcuminoids: An Updated Review of Clinical Trials
- Review, Var, NA
RadioS↑, curcumin has been shown to enhance the efficacy of the conventional anti‐cancer modalities such as radiation and chemotherapy.
ChemoSen↑,
MMPs↓, By suppressing the expression of matrix metalloproteinases (MMPs), which are enzymes that break down the extracellular matrix and promote cancer cell invasion and metastasis
TumMeta↓,
TumCI↓,
Inflam↓, Inflammation and the advancement of cancer are linked to the NF‐κB signaling pathways, which are also suppressed by curcuminoids.
NF-kB↓,
BioAv↓, curcumin's low bioavailability limits its therapeutic use.
BioAv↑, may be overcome due to recent developments in drug delivery technologies, such as curcumin‐loaded nanoparticles.
MAPK↓, Curcuminoids prevent the activation of a variety of signaling pathways, including the MAPK, PI3K/Akt, and NF‐kB pathways,
PI3K↓,
Akt↓,
*ROS↓, Many studies have pointed out curcumin's potential to reduce oxidative stress markers significantly in various biological models
*MDA↓, significant decrease in the level of MDA in treated animals was observed, which indicated that curcumin treatment delays the process of lipid peroxidation.
*lipid-P↓,
*Half-Life↓, Curcumin has a short biological half‐life and is poorly soluble in water, which allows understanding the low bioavailability of curcumin after oral administration.
mTOR↓, In breast cancer, curcumin mainly targets PI3K/Akt/mTOR

6219- CUR,    Natural Products and Altered Metabolism in Cancer: Therapeutic Targets and Mechanisms of Action
- Review, Var, NA
PI3K↓, blocking the PI3K/Akt pathway and its downstream NF-κB protein expression
Akt↓,
NF-kB↓,
BioAv↑, Piperine is a bioavailability enhancer for several chemotherapeutic agents, such as resveratrol and curcumin.
GSK‐3β↓, blocking the ILK/GSK-3β/slug signaling pathway.
Slug↓,
Cyt‑c↑, 0, 9, 18 of piperine and 36 µM curcumin for 24 h Leukemia (HL60) Release of mitochondrial cytochrome-c, which further initiates caspase-9/3 mediated cell apoptosis.
Casp3↑,
Casp9↑,

6216- CUR,    Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials
- Review, Var, NA
TumCG↓, Curcumin can prevent tumor growth, angiogenesis, epithelial–mesenchymal transition, invasion, and metastasis by modulating the expression of tumor-related non-coding RNA (ncRNA)
angioG↓,
EMT↓,
TumCI↓,
TumMeta↓,
*GutMicro↑, curcumin plays a crucial role in regulating the gut microbiota via biotransformation of curcumin and its metabolites.
*BioAv↓, one of the primary drawbacks of taking curcumin alone is its low bioavailability, which appears to be caused by poor absorption, fast metabolism, and excretion
*HO-1↑, Curcumin is an efficient inducer of hemoxygenase-1 and a powerful inhibitor of reactive oxygen-generating enzymes, such as cyclooxygenase (COX), inducible nitric oxygen synthase (iNOS), lipoxygenase, and xanthine dehydrogenase/oxidase
*ROS↓,
*COX2↓,
*iNOS↓,
PKCδ↓, Curcumin is also a powerful inhibitor of protein kinase C (PKC), tyrosine kinase, epidermal growth factor receptor (EGFR), and IB kinase.
EGFR↓,
NF-kB↓, It suppresses NF-κB activation and the expression of oncogenes, such as c-jun, c-fos, c-myc, Akt, PI3K, cyclin-dependent kinase (CDK)
cJun↓,
cFos↓,
cMyc↓,
Akt↓,
PI3K↓,
CDK4↓,
*TNF-α↓, Continuous supplementation with nanocurcumin (two 40 mg capsules/day after a meal) for 3 months suppressed expression of inflammatory tumor necrosis factor-alpha (TNF-α), high sensitive protein with C-reactive protein (CRP), and interleukin-6 (IL-6)
*CRP↓,
*IL6↓,
MMP9↓, curcumin suppressed metastasis to the lung by suppressing NF-κB, MMP-9, COX-2, and vascular endothelial growth factor (VEGF) expression.
VEGF↓,
JAK↓, Curcumin remarkably inhibits JAK/STAT signaling by downregulating pro-inflammatory interleukins, such as IL-1, IL-2, IL-6, IL-8, IL-12, and MCP-1.
STAT↓,
IL1↓,
IL2↓,
IL6↓,
IL8↓,
IL12↓,
MCP1↓,
Apoptosis↑, It promotes apoptosis and ER stress by targeting phosphorylated protein kinase-like ER-resident kinase,
ER Stress↑,
5LO↓, inhibiting lipoxygenase and xanthine oxidase activity
XO↓,
*NRF2↑, The expression of nuclear factors erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) is boosted by curcumin
*HO-1↑,
*AChE↓, Curcumin also inhibits the key enzyme acetylcholinesterase (AChE) and p300, a positive regulator of the Wnt/β-catenin pathway
*neuroP↑, Curcumin has also been suggested to prevent and cure neurotoxicity by replenishing dopamine and 3,4-dihydroxyphenylacetic acid levels.
*glucose↓, remarkably lowers blood glucose levels and improves insulin resistance by reducing hepatic glucose synthesis, inhibiting inflammatory reactions produced by hyperglycemia,
*GLUT2↑, boosting glucose transporters 2 (GLUT2), 3 (GLUT3), and 4 (GLUT4) gene expression, enhancing glucose uptake, and activating the AMPK signaling pathway.
*GLUT3↑,
*GLUT4↑,
*GlucoseCon↑,
*AMPK↑,
*BMD↑, Supplementation with nanomicelle curcumin (80 mg) alone or in combination with Nigella sativa oil (1000 mg) for 2–6 months increased plasma levels of miRNA-21 in postmenopausal women with low bone mass density.
*MDA↓, (1000 mg/day) for 8 weeks reduced serum levels of malondialdehyde (MDA) and high-sensitivity CRP (hs-CRP) and increased the total antioxidant capacity in 81 healthy postmenopausal women
*eff↑, Loriczova et al. demonstrated that iron (18 mg and 65 mg) supplementation along with curcumin (500 mg) reduces iron-induced systemic inflammation by reducing plasma levels of TNF-α
eff↑, high-dose vitamin C (25–100 g/day) along with oral nutrient supplementation including curcumin (1–3 g/day) had improved QoL and survival
P53↑, Curcumin was also reported to induce p53 and Bax expression in patients with colorectal cancer, causing apoptosis and DNA fragmentation and suppressing TNF-α and Bcl-2.
BAX↑,
DNAdam↑,
Bcl-2↓,
CSCs↓, The combination of curcumin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in colorectal liver metastases reduced stem cell markers, such as aldehyde dehydrogenase and CD133.
ALDH↓,
CD133↑,

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

6212- CUR,  Rad,    Radiosensitization and Radioprotection by Curcumin in Glioblastoma and Other Cancers
- Review, Var, NA
RadioS↑, Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent
*radioP↑, curcumin has been found to possess radioprotective properties, since it can lessen inflammatory toxicities associated with radiotherapy, like dermatitis, mucositis, and myelosuppression
EGFR↓, Curcumin can suppress the gene expression of EGFR, and downregulate the TGF-β pathway, thus leading to inhibition of cancer-associated fibroblasts (CAF)
TGF-β↓,
ROS↑, Curcumin can induce ROS generation and suppress DNA repair machinery, thus leading to increased radiation-induced cell death
P53↑, upregulation of both the expression and activity of p53, regulation of the anti-apoptotic PI3K signaling, and suppression of the activity of NF-κB and COX-2
PI3K↓,
NF-kB↓, curcumin increased radiation-induced apoptotic death primarily through inhibition of the NF-κB signaling pathway
COX2↓,
EMT↓, Curcumin was found to suppress radiation-induced EMT resulting in the inhibition of NSCLC migration and invasion
Hif1a↓, inhibition of the expression of both hypoxia-inducible factor 1-alpha (HIF-1a) and heat shock protein 90 (HSP90) proteins and increase in the levels of ROS
HSP90↓,
mTOR↓, In cervical cancer, curcumin has been studied as a potent mTOR inhibitor when given together with irradiation.
*Catalase↑, 40 rats were exposed to curcumin 1 day before irradiation to 3 consecutive days after irradiation, the levels of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA), were found to be considerably eleva
*SOD↑,
*MDA↑,
*Wound Healing↑, treatment with curcumin stimulated wound healing,
*hepatoP↑, curcumin treatment prior to radiation can prevent liver damages, mainly through the modulation of the NF-κB pathway and reduction of oxidative stress (upregulation of SOD, CAD and GSH levels in the curcumin-treated group)
*NF-kB↓,
*ROS↓,

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.

3576- CUR,    Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease
- Review, AD, NA
*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

457- CUR,    Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling
- in-vitro, GC, SGC-7901 - in-vitro, GC, BGC-823
TumCP↓,
Apoptosis↑,
TumAuto↑,
P53↑,
PI3K↓,
P21↑,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
Bcl-xL↓,
LC3I↓, LC3I
BAX↑,
Beclin-1↑,
cl‑Casp3↑,
cl‑PARP↑,
LC3II↑,
ATG3↑,
ATG5↑,

468- CUR,  5-FU,    Gut microbiota enhances the chemosensitivity of hepatocellular carcinoma to 5-fluorouracil in vivo by increasing curcumin bioavailability
- vitro+vivo, Liver, HepG2 - vitro+vivo, Liver, 402 - vitro+vivo, Liver, Bel7
Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
PI3k/Akt/mTOR↓,
p‑PI3K↓,
Bacteria↑, gut microbiota: Lactobacillus, Epsilonbacteraeota, Helicobacterac-eae, Campylobacterales, Helicobacter, Escherichia-shigella, Bifidobacterium, Campylobacteria
cl‑Casp3↑,

435- CUR,    Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway
- in-vitro, Lung, A549
Apoptosis↑,
TumAuto↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
Beclin-1↑,
p62↓,
PI3K↓,
Akt↓,
mTOR↓,
p‑Akt↓,
p‑mTOR↓,

15- CUR,  UA,    Effects of curcumin and ursolic acid in prostate cancer: A systematic review
- Review, Pca, NA
NF-kB↝, involve NF-κB, Akt, androgen receptors, and apoptosis pathways.
Akt↝, see figure 5
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↝,

4827- QC,  CUR,    Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin
- Review, Var, NA
*AntiCan↑, their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions.
*Inflam↓,
*Bacteria↓,
*AntiDiabetic↑,
*ROS↓, suppression of ROS formation via the inhibition of the enzyme activities involved in their production, or via scavenging ROS directly by acting as hydrogen donors; the chelation of the metal ions that induce ROS production;
*SOD↑, quercetin can eliminate free radicals and help maintain a stable redox state in cells by increasing anti-oxidant enzymes, such as superoxide dismutase (SOD), and catalase expressions, as well as the level of reduced glutathione (GSH)
*Catalase↑,
*GSH↑,
*NRF2↑, Quercetin can protect human granulosa cells from oxidative stress by inducing Nrf2 expression at both the gene and protein levels, which in turn induces the anti-oxidant thioredoxin (Trx) system.
*Trx↑,
*IronCh↑, pure curcumin, a metal chelator, directly removes ROS and regulates numerous enzymes.
*MDA↑, It has the potential to reduce the concentration of malondialdehyde (MDA) in serum and increase the total anti-oxidant potential
cycD1/CCND1↓, Cyclin D1 expression was significantly decreased in quercetin-treated ovarian SKOV-3 cells, but not in cisplatin (CDDP)-resistant SKOV3/CDDP cells.
PI3K↓, The levels of PI3K and phospho-Akt were decreased in curcumin-treated SKOV3 cells, which in turn increased caspase-3 and Bax levels.
Casp3↑,
BAX↑,
ChemoSen↑, Curcumin enhanced the efficacy of chemotherapy in colorectal cancer cells.
ROS↑, suggesting that quercetin-induced cytotoxicity and autophagy were initiated by the generation of ROS
eff↑, quercetin or curcumin with chemotherapeutic agents, as shown below, considerably enhances the antitumor potencies of doxorubicin (DOX) and cisplatin.
MMP↓, The synergistic treatment with curcumin and quercetin inhibited the cell proliferation associated with the loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c, a decrease in AKT and ERK phosphorylation in MGC803 human gastric
Cyt‑c↑,
Akt↓,
ERK↓,


Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   NRF2↝, 1,   ROS↑, 5,   ROS↝, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   PI3k/Akt/mTOR↓, 1,  

Cell Death ⓘ

Akt↓, 8,   Akt↝, 1,   p‑Akt↓, 2,   Apoptosis↑, 5,   Apoptosis↝, 1,   BAX↑, 3,   BAX↝, 1,   Bcl-2↓, 2,   Bcl-2↝, 1,   Bcl-xL↓, 1,   Bcl-xL↝, 1,   Casp↑, 1,   Casp3↑, 3,   Casp3↝, 1,   cl‑Casp3↑, 2,   Casp9↑, 1,   Cyt‑c↑, 3,   Cyt‑c↝, 1,   Ferroptosis↑, 1,   JNK↝, 1,   MAPK↓, 2,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   HATs↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   ATG5↑, 1,   Beclin-1↑, 2,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3I↓, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMTs↓, 1,   P53↑, 4,   P53↝, 1,   PARP↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   Cyc↝, 1,   cycD1/CCND1↓, 1,   cycD1/CCND1↝, 1,   P21↑, 1,   P21↝, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   Axin2↑, 1,   CD133↑, 1,   cFos↓, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   FOXO1↓, 1,   GSK‐3β↓, 3,   HDAC↓, 1,   HH↓, 1,   mTOR↓, 6,   mTOR↝, 1,   p‑mTOR↓, 2,   NOTCH↓, 2,   PI3K↓, 10,   PI3K↝, 1,   p‑PI3K↓, 1,   PTEN↑, 1,   PTEN↝, 1,   STAT↓, 1,   STAT3↓, 2,   TumCG↓, 2,   Wnt↓, 3,  

Migration ⓘ

5LO↓, 1,   AP-1↝, 1,   MMP2↝, 1,   MMP9↓, 1,   MMPs↓, 2,   PKCδ↓, 1,   Slug↓, 1,   TGF-β↓, 1,   TumCI↓, 4,   TumCP↓, 1,   TumMeta↓, 4,   β-catenin/ZEB1↓, 3,   β-catenin/ZEB1↝, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 2,   EGFR↝, 1,   Hif1a↓, 1,   VEGF↓, 2,   VEGF↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 2,   COX2↝, 1,   IL1↓, 1,   IL12↓, 1,   IL2↓, 1,   IL6↓, 1,   IL6↝, 1,   IL8↓, 1,   Inflam↓, 1,   JAK↓, 3,   MCP1↓, 1,   NF-kB↓, 7,   NF-kB↝, 1,   PGE2↓, 1,   PSA↝, 1,   TNF-α↝, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↓, 1,  

Protein Aggregation ⓘ

XO↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↝, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   ChemoSen↑, 4,   eff↑, 3,   Half-Life↓, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

cardioP↑, 1,  

Infection & Microbiome ⓘ

Bacteria↑, 1,  
Total Targets: 131

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 3,   GSH↑, 2,   GSTs↑, 1,   HO-1↑, 4,   HO-2↓, 1,   lipid-P↓, 1,   MDA↓, 2,   MDA↑, 2,   NRF2↑, 4,   ROS↓, 6,   SOD↑, 3,   Trx↑, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↑, 1,   IronCh↑, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cytoP450↓, 1,   glucose↓, 1,   GlucoseCon↑, 1,   GLUT2↑, 1,   LDL↓, 1,  

Cell Death ⓘ

Akt↑, 1,   Bcl-2↑, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT3↑, 1,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL1↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 4,   NF-kB↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   ChAT↑, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 1,   eff↑, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

BMD↑, 1,   CRP↓, 1,   Ferritin↑, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 2,   radioP↑, 2,   Wound Healing↑, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 60

Scientific Paper Hit Count for: PI3K, Phosphatidylinositide-3-Kinases
13 Curcumin
1 Radiotherapy/Radiation
1 5-fluorouracil
1 Ursolic acid
1 Quercetin
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#:252  State#:%  Dir#:%
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