Curcumin / ChemoSen 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):

Suppression of NF-κB / STAT3 inflammatory-survival signaling, reducing cytokine, COX-2, iNOS, anti-apoptotic, invasion, and treatment-resistance programs.
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.
Mitochondrial injury and intrinsic apoptosis, including mitochondrial membrane potential loss, cytochrome-c release, caspase activation, PARP cleavage, and ER-stress/UPR involvement.
PI3K/AKT/mTOR and MAPK pathway modulation, contributing to growth arrest, autophagy modulation, apoptosis sensitization, and reduced survival signaling.
Wnt/β-catenin, Hedgehog/GLI, Notch, and cancer-stem-cell suppression, reducing stemness, EMT, invasion, and recurrence-associated phenotypes in models.
Hypoxia / HIF-1α and glycolysis inhibition, including reduced GLUT1, HK2, LDHA, PKM2, lactate/ECAR, and Warburg-like metabolic support in selected models.
Anti-angiogenic and anti-metastatic modulation, including VEGF, MMPs, uPA, CXCR4/SDF-1, TGF-β/α-SMA, FAK, and EMT-related axes.
Epigenetic and transcriptional reprogramming, including reported HDAC, DNMT, EZH2, Sp-family, p53, and microRNA-related effects.
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.
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

ChemoSen, chemo-sensitization: Click to Expand ⟱

Source:

Type:

The effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”.

Possible Chemo-Sensitizers:
-Curcumin
-Resveratrol
-EGCG
-Quercetin
-Genistein
-Berberine
-Piperine: alkaloid from black pepper
-Ginsenosides: active components of ginseng
-Silymarin
-Allicin
-Lycopene
-Ellagic acid
-Caffeic acid phenethyl ester
-flavopiridol
-oleandrin
-Ursolic acid
-butein
-Betulinic acid

Scientific Papers found: Click to Expand⟱

1426-

Bos,

CUR,

Chemo,

Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer

in-vivo,

CRC,

10um(cur), 30uM(AKBA)

mouse

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

RKO

in-vitro,

CRC,

SW480

in-vitro,

RCC,

SW-620

in-vitro,

RCC,

HT-29

in-vitro,

CRC,

Caco-2

miR-34a↑, curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells
miR-27a-3p↓,
TumCG↓,
BAX↑,
Bcl-2↓,
PARP1↓,
TumCCA↑,
Apoptosis↑,
cMyc↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
ChemoSen↑, combined treatment further increased the inhibitory effects
miR-34a↑, miR-34a expression was upregulated by curcumin and further elevated by concurrent treatment with curcumin and AKBA in HCT116 cell
miR-27a-3p↓,

2015-

CAP,

CUR,

urea,

Anti-cancer Activity of Sustained Release Capsaicin Formulations

Review,

Var,

AntiCan↑, Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers.
TumCG↓,
angioG↓,
TumMeta↓,
BioAv↓, clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties
BioAv↓, capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting
BioAv↑, All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems.
selectivity↑, Most importantly, these long-acting capsaicin formulations selectively kill cancer cells and have minimal growth-suppressive activity on normal cells.
EPR↑, The EPR effect is a mechanism by which high–molecular drug delivery systems (typically prodrugs, liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues
eff↓, The efficiency of such extravasation is maximum when the size of the liposomes less than 200 nm The CAP-CUR-GLY-GAL-LIPO were spherical in shape with a narrow range of size distribution ranging from 135–155nm
ChemoSen↑, The chemosensitization and anti-tumor activity of capsaicin involves multiple molecular pathways
Dose∅, oral, Intravenous (IV), and Intraperitoneal (IP) options
Half-Life∅, oral metabolized in 105mins, T1/2in blood=25mins.
eff↑, presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin

4831-

CUR,

The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity

in-vitro,

NA,

*NRF2↑, We reported that both polyphenols show antioxidant and oto-protective activity in the cochlea by up-regulating Nrf-2/HO-1 pathway and downregulating p53 phosphorylation.
*P53↓,
*NF-kB↓, only curcumin is able to influence inflammatory pathways counteracting NF-κB activation
ROS↑, In human cancer cells, curcumin converts the anti-oxidant effect into a pro-oxidant and anti-inflammatory one
Inflam↓,
ChemoSen↑, Curcumin exerts permissive and chemosensitive properties by targeting the cisplatin chemoresistant factors Nrf-2, NF-κB and STAT-3 phosphorylation.

4709-

CUR,

Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways

Review,

Var,

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↓,

4675-

CUR,

Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines

in-vitro,

NSCLC,

A549

10–40 µM

ChemoSen↑, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis.
CSCs↓, Curcumin enhances the sensitivity of the CSC subpopulation of CD166+/EpCAM+ cells to cisplatin-induced apoptosis
EpCAM↓, curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation
TumCCA↓, combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway.
VEGF↓, curcumin markedly decreased the metastasis of breast tumour cells to the lung and suppressed the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9)
MMP9↓,
toxicity↓, Furthermore, curcumin has been found to be safe when administered at ≤10 g/day in humans

4671-

CUR,

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy

in-vitro,

CRC,

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↓,

6227-

CUR,

Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations

Review,

Var,

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

6225-

CUR,

Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance

Review,

Var,

ox-Trx1↑, Curcumin increases Trx1 oxidation and subsequent apoptosis in prostate cancer cells [95].
TrxR1↓, (curcuminoid B63) has been shown to induce ROS-mediated paraptosis-like cell death by targeting TrxR1 in gastric cancer cells
TrxR↓, curcumin-induced inhibition of TrxR may depend on its Michael acceptor function.
ROS↑, leads to dramatic pro-oxidant effects, the induction of NOX activity, and the production of ROS
GSH/GSSG↓, significant decrease in the GSH/GSSG ratio was observed in lung cancer cells after treatment with curcumin
eff↓, NAC partially or completely reversed these effects, suggesting that ROS generation may be the underlying cause of curcumin-induced cell death.
Fenton↑, curcumin reduces Cu(II) to Cu(I) and leads to the formation of H2O2, which further reacts with Cu(I) through the Fenton reaction to produce •OH.
H2O2↑,
*NRF2↑, curcumin pretreatment significantly increases Nrf2 in the nucleus and decreases the expression of Keap1, as well as reverses the doxorubicin-induced reduction of HO-1 and NQO1, which provides a rational mechanism against doxorubicin-induced neurotoxi
*Keap1↓,
*HO-1↑,
*NQO1↑,
ChemoSen↑, The cisplatin and curcumin coloaded liposome system extends the drug duration and promotes drug accumulation in tumours.

6223-

CUR,

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects

Review,

Var,

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↓,

6222-

CUR,

Anticancer Molecular Mechanisms of Curcuminoids: An Updated Review of Clinical Trials

Review,

Var,

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

6221-

CUR,

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer

Review,

Var,

NF-kB↓, NF-Kβ suppression from Cur interaction led to the identification of Cur’s immunomodulatory effects
Imm↑, on various cytokines and immune related proteins such as IL-6, TNF-α, and PD-L1 and is suggested as a potential adjuvant treatment for immunotherapy
*TAC↑, In clinical trials, Cur is shown to increase total antioxidant capacity (TAC) and decrease malondialdehyde.53
*MDA↓,
ROS↑, increases overall ROS accumulation in SiHa cervical cancer cells resulting in increased autophagy and G2/M phase cell cycle arrest.54
TumAuto↑,
TumCCA↑,
Keap1↑, activate KEAP1/NRF2/ARE pathways and serve as an effective therapeutic especially in combination with 5-FU
ChemoSen↑,
ER Stress↑, administration of 1g resulted in ROS production, G1 cell cycle phase arrest, and increased ER-stress which was reversed upon addition of NAC, an ROS scavenging agent
eff↓, reversed upon addition of NAC
TrxR↓, Non-small cell lung cancer cell lines showed marked increases in apoptosis and ferroptosis driven by the analogs ability to generate ROS through TrxR inhibition.
STAT3↓, analog WZ26 increased ROS and cell death in cholangiocarcinoma via STAT3 inhibition
*BioAv↓, Studies with doses as high as 12 g/day still resulted in small amounts of traceable plasma Cur, mostly due to low absorption in the small intestine and rapid elimination in the body via the gall bladder.

6215-

CUR,

Curcumin: biochemistry, pharmacology, advanced drug delivery systems, and its epigenetic role in combating cancer

Review,

Var,

*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

6214-

CUR,

Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve

TumCD↓, Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability.
TumCI↓,
*Inflam↓, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc.
*antiOx↓,
*AntiTum↓,
NF-kB↓, Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2),
COX2↓,
Casp9↓, promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells.
ROS↑, Curcumin can induce lethal levels of reactive oxygen species (ROS) in tumors
BioAv↑, Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy.
RadioS↑, Figure 1, Curcumin Increases Radiosensitivity of Tumor
ChemoSen↑,
Imm↑,
PhotoS↑, Curcumin Mediates the Antitumor Effect of PDT
sonoS↑, Curcumin Mediates the Antitumor Effect of SDT
5LO↓, down-regulating the activities of cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inducible nitric oxide synthase (iNOS) and so on, reducing the production of proinflammatory cytokines such as IL-2, tumor necrotic factor-α (TNF-α),
iNOS↓,
IL2↓,
TNF-α↓,
Casp9↑, activating intracellular caspase-9 and caspase-3, reducing the expression of p53, inhibiting Bcl2, and promoting the expression of Bax and down-regulating the proportion of Bcl2/Bax
Casp3↑,
Bcl-2↓,
BAX↑,
Apoptosis↑, promote apoptosis by activating caspase-4 and stimulating the Endoplasmic reticulum (ER) stress pathway and mitochondria stress pathway in tumor cells [
ER Stress↑,
cycD1/CCND1↓, It reduces the expression of cyclin D1, cyclin kinase-dependent kinase 2 (CDK2), cdc2/cyclin B complex, and other cell cycle-related proteins,
CDK2↓,
CycB/CCNB1↓,
TumCCA↑, blocks tumor cells from G1 / S phase and G2 / M phase, thus exerting an antitumor effect
MMPs↓, curcumin inhibits tumor invasion and metastasis by inhibiting NF-κB and other signaling pathways, such as chemokine and matrix metalloproteinases (MMPs)
*radioP↑, Curcumin can effectively treat and prevent radiation adverse reactions such as radiation dermatitis and radiation pneumonia by reducing the expression of inflammatory factors such as fibrotic cytokines, TNF-α, and IL-1, inhibiting NF-κB signal pathwa
chemoP↑, Protective Effect of Curcumin on Side Effects of Chemotherapy
hepatoP↑, urcumin alleviates the hepatotoxicity caused by chemotherapy through anti-inflammation and antioxidation, reducing the level of liver fibrosis and blood lipids [
cardioP↑, Using curcumin to reduce the cardiotoxicity of chemotherapy can improve the therapeutic effect of tumors and patients' prognosis and quality of life.
eff↑, Curcumin Enhances the Therapeutic Effect of Immunotherapy
PhotoS↑, it has the potential to be a new photosensitizer
eff↑, Curcumin nanoparticles with functions of relieving hypoxia and consuming GSH could improve the ability of curcumin to induce ROS and promote ROS- mediated tumor cell death
ROS↑,
GSH↓,

6211-

CUR,

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer

Review,

Var,

HIF-1↓, Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF).
VEGF↓, Curcumin suppresses the HIF-1 pathway under hypoxia, which decreases VEGF expression in both tumour and stromal cells and suppresses angiogenesis.
angioG↓, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia.
RadioS↑, continued interest in curcumin is the molecules’ modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours.
ChemoSen↑, Combining cisplatin with curcumin promotes cell apoptosis through the YWHAG pathway and its interaction with HIF-1α, affecting the pentose phosphorylation pathway [
other↝, Cancer patients with hypoxia in their tumours have a poorer prognosis and are at greater risk of metastasis
Apoptosis↑, Curcumin exerts its unique anti-tumour efficacy primarily via pleiotropic functions resulting in apoptosis and decreased tumour cell growth and metastasis
TumCG↓,
TumMeta↓,
BioAv↓, However, due to its low water solubility and low chemical stability, curcumin’s use is limited.
COX2↓, abrogate the proliferation of pancreatic cancer cells through inhibition of COX-2, CD-31, VEGF, and IL-8 and suppression of TGF-β via NF-κB and HIF-1α downregulation
CD31↓,
IL8↓,
TGF-β↓,
NF-kB↓,
JAK2↓, Curcumin application reduced tumourspheres of H460 cells via inhibition of the JAK2/STAT3 signalling pathway
STAT3↓,

6209-

CUR,

Curcumin as a complementary treatment in oncological therapy: a systematic review

other↝, The findings of the included studies indicate that the administration of curcumin may offer a potential benefit with respect to oral symptoms and weight loss.
eff↓, Overall, 6 studies found no significant effect of curcumin in all or almost all investigated endpoints
*BioAv↓, Due to its low bioavailability, high doses seem necessary when using pure curcumin for it to be detected in the plasma
ChemoSen↓, In vitro or in vivo studies indicate an interaction between curcumin and various chemotherapeutic agents, with curcumin reducing the effect, depending on dosage and time of curcumin administration

6205-

CUR,

Clinical trials on curcumin in relation to its bioavailability and effect on malignant diseases: critical analysis

Review,

Var,

BioAv↓, After oral ingestion, only a small portion of curcumin is absorbed. The absorbed portion is metabolized at a pH of > 7 within 20 min
Half-Life↓, problem of curcumin bioavailability can be attributed to its low absorption, rapid metabolism, short half-life, and low tissue distribution
COX2↓, COX-2 expression levels decreased significantly after oral administration of 8 g curcumin/day
ChemoSen↑, observed benefits of the treatment group with curcumin paclitaxel combination remained (Saghatelyan et al. 2020). A slightly increased PFS was observed in the curcumin group compared to the placebo group.
cachexia↓, average gain in muscle mass of 0.46 kg muscle mass in the patients treated with curcumin, after the interval of 8 weeks (Thambamroong et al. 2022). Patients receiving placebo lost an average of 1.05 kg of muscle mass
NF-kB↓, Inhibition of the NF-κB pathway has also been observed in patients with pancreatic cancer

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

2308-

CUR,

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells

in-vitro,

Liver,

HepG2

GlucoseCon↓, Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production
lactateProd↓,
ECAR↓,
NO↓,
ROS↑, Curcumin favors the ROS production in HepG2 cells in normal as well as hyperglycemic conditions. ROS production was detected in cancer cells treated with curcumin, or doxorubicin, or their combinations in NG or HG medium for 24 h
HK2↓, HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, tr
PFK1↓,
GAPDH↓,
PKM2↓,
LDHA↓,
FASN↓,
GLUT1↓, Curcumin treatment was able to significantly decrease the expression of GLUT1, HKII, and HIF-1α in HepG2 cells either incubated in NG or HG medium.
MCT1↓,
MCT4↓,
HCAR1↓,
SDH↑, Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition
ChemoSen↑, Curcumin Prevents High Glucose-Induced Chemoresistance
ROS↑, Treatment of cells with doxorubicin in presence of curcumin was found to cooperatively augment the ROS level in cells of both NG and HG groups.
BioAv↑, Curcumin Favors Drug Accumulation in Cancer Cells
P53↑, An increased expression of p53 in curcumin-treated cells can be suggestive of susceptibility towards cytotoxic action of anticancer drugs
NF-kB↓, curcumin has therapeutic benefits in hyperglycemia-associated pathological manifestations and through NF-κB inhibition
pH↑, Curcumin treatment was found to resist the lowering of pH of culture supernatant both in NG as well in HG medium.

1411-

CUR,

Cisplatin,

Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Review,

Var,

ChemoSen↑, decreasing CP's adverse impacts and improving its antitumor
*ROS↓, Curcumin administration reduces ROS levels to prevent apoptosis in normal cells.
*NF-kB↓, curcumin can inhibit inflammation via down-regulation of NF-κB to maintain the normal function of organs.
TumCCA↑,

1485-

CUR,

Chemo,

Rad,

Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs

Review,

Var,

ChemoSen↑, Such effects of curcumin were due to its ability to sensitize cancer cells for increased production of ROS
NF-kB↓, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt
*STAT3↓, curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-kB, STAT3, COX2, Akt,
*COX2↓,
*Akt↓,
*NRF2↑, The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase
*HO-1↑,
*GPx↑,
*NADPH↑,
*GSH↑, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase)
*ROS↓, dietary curcumin can inhibit chemotherapy-induced apoptosis via inhibition of ROS generation and blocking JNK signaling
*p300↓, inhibit p300 HAT activity
radioP↑, radioprotector for normal organs
chemoP↑, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity.
RadioS↑,

1486-

CUR,

Curcumin and lung cancer--a review

Review,

Lung,

RadioS↑,
ChemoSen↑,

1487-

CUR,

Relationship and interactions of curcumin with radiation therapy

Review,

Var,

RadioS↑, overall level of evidence for curcumin as a radiosensitizer and radioprotector is low, it must be recognized that risks of adverse effects are exceedingly low, and clinicians may need to judge the yet-unproven rewards with low toxicity risks.
ChemoSen↑,
NF-kB↓, suppressing NF-κB
radioP↑, substantial volume of evidence exists that curcumin is a radiosensitizer of multiple cancers as well as a radioprotector of several normal tissues.
BioAv↓, Further research is greatly needed to strengthen curcumin’s major weakness - poor gastrointestinal absorption leading to low oral bioavailability.
*toxicity↓, curcumin is extremely safe and not harmful to the cancer patient undergoing radio(chemo)therapy.

1488-

CUR,

Anti-Cancer and Radio-Sensitizing Effects of Curcumin in Nasopharyngeal Carcinoma

RadioS↑,
ChemoSen↑,

133-

CUR,

Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

miR-143↑, Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration.
PDK1↓, curcumin treatment inhibited PGK1 expression
FOXD3↑, Curcumin time-dependently upregulated FOXD3, which accounted for the escalating miR-143 levels with the duration of curcumin treatment.
TumCP↓, Furthermore, we showed that silencing miR-143 abrogated the effect of curcumin in inhibiting cell proliferation and migration.
TumCMig↓,
*Inflam↓, pharmaceutical properties of curcumin include antiinflammatory, antioxidant, chemo-preventative, and chemotherapeutic properties
*antiOx↑,
*chemoPv↑,
RadioS↑, underlying mechanism of curcumin in prostate cancer therapy, potentiating the clinical utility of curcumin as a chemo-preventive, chemotherapeutic, radio-, and drug-sensitizing agent.
ChemoSen↑,

136-

CUR,

docx,

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer

in-vitro,

Pca,

DU145

 5-50uM

 19.2 nM(docx), 32.3 μM(CUR)

20 μM curcumin and 10 nM docetaxel significantly decrease (2.7 fold) the proliferation

in-vitro,

Pca,

PC3

 46 nM(docx), 36.1 μM(CUR)

combined treatment decrease (3.2 fold)

Bcl-2↓, combined treatment with curcumin with docetaxel down-regulates the expression of the anti-apoptotic proteins BCL-2, BCL-XL and MCL-1 in DU145 and PC3 cells
Bcl-xL↓,
Mcl-1↓,
BAX↑, Whereas, the expression of the pro-apoptotic markers BAK and BID were significantly up-regulated in curcumin with docetaxel treated group compared to curcumin and docetaxel-treated group alone
BID↑,
PARP↑, combined treatment with curcumin and docetaxel in DU145 and PC3 cells enhanced proteolysis of PARP compared
NF-kB↓, Curcumin blocks NF-κB activation in docetaxel-treated PCa cells
CDK1↓, treatment of curcumin and docetaxel significantly reduced the expression of the proliferation marker CDK-1 and inflammatory marker COX-2
COX2↓,
RTK-RAS↓,
PI3K/Akt↓, combined treatment of curcumin and docetaxel reduced the expression of PI3K, phospho-AKT, EGFR and HER2 in both DU145 and PC3 cells
EGFR↓,
HER2/EBBR2↓, docetaxel in combination with curcumin down-regulates the expression of HER2 and EGFR resulting inhibition of the expression of PI3K kinase and phospho-AKT
P53↑,
ChemoSen↑, The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone.

12-

CUR,

Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells

in-vitro,

MB,

DAOY

 20 uM

HH↓, Curcumin inhibits the Sonic Hedgehog signaling pathway
Shh↓, curcumin inhibited the Shh-Gli1 signaling pathway by downregulating the Shh protein
Gli1↓,
PTCH1↓,
cMyc↓,
n-MYC↓,
cycD1/CCND1↓,
Bcl-2↓,
NF-kB↓,
Akt↓,
β-catenin/ZEB1↓, curcumin reduced the levels of beta-catenin
survivin↓,
Apoptosis↑, Consequently, apoptosis was triggered by curcumin through the mitochondrial pathway via downregulation of Bcl-2, a downstream anti-apoptotic effector of the Shh signaling.
ChemoSen↑, curcumin enhances the killing efficiency of nontoxic doses of cisplatin and gamma-rays.
RadioS↑,
eff↑, we present clear evidence that piperine, an enhancer of curcumin bioavailability in humans

150-

NRF,

CUR,

docx,

Subverting ER-Stress towards Apoptosis by Nelfinavir and Curcumin Coexposure Augments Docetaxel Efficacy in Castration Resistant Prostate Cancer Cells

in-vitro,

Pca,

C4-2B

 NFR (5 µM), CUR (5 µM),DTX 10nM

 CRPC

p‑Akt↓,
p‑eIF2α↑, phosphorylated
ER Stress↑, Acute exposure (3–9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3.
ATF4↑, 3-drug combination rapidly enhances ER-stress associated death sensors, CHOP, ATF-4 and TRIB3 in C4-2B cells
CHOP↑,
TRIB3↑,
ChemoSen↑, subverting ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can chemosensitize the CRPC cells to DTX therapy.
Casp3↑, NFR or CUR alone could increase Caspase-3 activity in DTX exposed cells
cl‑PARP↑, PARP cleavage assays further confirmed this differential effect of drug combination on apoptotic cell death. In C4-2B cells, a 9-fold increase was observed
BID↑, 3-drug combination rapidly increases ER-stress transducers, BiP, eIF2µ and Xbp-1 in C4-2B cells
XBP-1↑,

4827-

QC,

CUR,

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

Review,

Var,

*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↓,

4667-

RES,

CUR,

SFN,

Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models

Review,

Var,

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 29 of 29

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 29

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 1, antiOx↑, 3, Catalase↑, 2, GPx↑, 1, GSH↑, 2, GSTs↑, 1, HO-1↑, 3, Keap1↓, 1, lipid-P↓, 1, MDA↓, 3, MDA↑, 1, NQO1↑, 1, NRF2↑, 5, ROS↓, 8, SOD↑, 3, TAC↑, 1, Trx↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Core Metabolism/Glycolysis ⓘ

cytoP450↓, 1, NADPH↑, 1,

Cell Death ⓘ

Akt↓, 1,

DNA Damage & Repair ⓘ

P53↓, 1,

Proliferation, Differentiation & Cell State ⓘ

p300↓, 1, STAT3↓, 1,

Angiogenesis & Vasculature ⓘ

NO↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1↓, 1, IL6↓, 1, Inflam↓, 6, NF-kB↓, 2, TNF-α↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 3, BioAv↑, 2, Half-Life↓, 1,

Clinical Biomarkers ⓘ

IL6↓, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, AntiTum↓, 1, chemoPv↑, 1, cognitive↑, 1, memory↑, 1, radioP↑, 2, toxicity↓, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 44

Scientific Paper Hit Count for: ChemoSen, chemo-sensitization

29 Curcumin
2 Chemotherapy
2 Docetaxel
1 Boswellia (frankincense)
1 Capsaicin
1 urea
1 Cisplatin
1 Radiotherapy/Radiation
1 nelfinavir/Viracept
1 Quercetin
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#:1106  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Curcumin / ChemoSen Cancer Research Results

Curcumin Cancer Mechanism Ranking

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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