Curcumin / toxicity Cancer Research Results

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

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
curcumin can act as a pro-oxidant when blue light is applied
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of survival and inflammatory transcription NF-κB is a primary, repeatedly validated curcumin target explaining pleiotropic downstream effects
2 STAT3 signaling ↓ STAT3 phosphorylation / activity ↔ or mild suppression Driver Loss of pro-survival and proliferative signaling STAT3 inhibition contributes to growth arrest, apoptosis sensitization, and reduced cytokine signaling in tumors
3 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Curcumin can act as a pro-oxidant in cancer cells with high basal stress while acting antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and caspase activation occur downstream of NF-κB/STAT3 and ROS effects
5 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ or adaptive suppression Secondary Reduced growth and anabolic signaling AKT/mTOR inhibition contributes to growth suppression and autophagy induction in cancer cells
6 Autophagy ↑ autophagy (protective or pro-death) ↑ adaptive autophagy Secondary Stress adaptation vs cell death Autophagy may be cytoprotective or cooperate with apoptosis depending on context and dose
7 HIF-1α / VEGF hypoxia–angiogenesis axis ↓ HIF-1α; ↓ VEGF ↔ minimal effect Secondary Anti-angiogenic pressure Suppression of hypoxia-driven transcription limits angiogenesis and tumor adaptation
8 Cell cycle regulation ↑ G2/M or G1 arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling and epigenetic effects rather than direct CDK inhibition
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT markers and protease activity limit invasive behavior
10 Epigenetic regulation (p300/CBP HAT activity) ↓ histone acetylation ↔ modest Secondary Transcriptional reprogramming Curcumin modulates chromatin via HAT inhibition rather than classic HDAC inhibition


toxicity, toxicity: Click to Expand ⟱
Source:
Type:
Toxicity
Scientific Papers found: Click to Expand⟱
5953- Cela,  CUR,    The Combination of Celastrol and Curcumin Enhances the Antitumor Effect in Nasopharyngeal Carcinoma by Inducing Ferroptosis
- vitro+vivo, NPC, NA
eff↑, TumCP↓, GPx4↓, eff↑, TumAuto↑, Ferroptosis↑, Dose↝, ACSL4↑, toxicity↓,
5995- Chit,  CUR,    Enhancement of anticancer activity and drug delivery of chitosan-curcumin nanoparticle via molecular docking and simulation analysis
- vitro+vivo, Var, NA
eff↑, EPR↑, DNAdam↑, TumCCA↑, ROS↑, toxicity↓,
4651- CUR,    Targeting cancer stem cells by curcumin and clinical applications
- Review, Var, NA
CSCs↓, *toxicity↓, *BioAv↝, chemoP↑,
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
ChemoSen↑, CSCs↓, EpCAM↓, TumCCA↓, VEGF↓, MMP9↓, toxicity↓,
2579- CUR,  ART/DHA,    Curcumin-Artemisinin Combination Therapy for Malaria
- in-vivo, NA, NA
OS↑, toxicity↓,
3575- CUR,    The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
- in-vivo, AD, NA
*antiOx↑, *ROS↓, *IL1β↓, *Aβ↓, *Inflam↓, *toxicity↓,
3574- CUR,    The effect of curcumin (turmeric) on Alzheimer's disease: An overview
- Review, AD, NA
*antiOx↑, *Inflam↓, *lipid-P↓, *cognitive↑, *memory↑, *Aβ↓, *COX2↓, *ROS↓, *AP-1↓, *NF-kB↓, *TNF-α↓, *IL1β↓, *SOD↑, *GSH↑, *HO-1↑, *IronCh↑, *BioAv↓, *Half-Life↝, *Dose↝, *BBB↑, *BioAv↑, *toxicity∅, *eff↑,
125- CUR,    Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway
- in-vitro, adrenal, H295R
CYP17A1↓, CYP19↓, *Nrf1↑, *NF-kB↓, angioG↓, Apoptosis↑, AR↓, toxicity↓, BioAv↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Ferroptosis↑, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 2,   EpCAM↓, 1,  

Migration ⓘ

MMP9↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EPR↑, 1,   VEGF↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CYP19↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   CYP17A1↓, 1,   Dose↝, 1,   eff↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   OS↑, 1,   toxicity↓, 5,  
Total Targets: 28

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   Nrf1↑, 1,   ROS↓, 2,   SOD↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Migration ⓘ

AP-1↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 2,   Inflam↓, 2,   NF-kB↓, 2,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

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

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   toxicity↓, 2,   toxicity∅, 1,  
Total Targets: 26

Scientific Paper Hit Count for: toxicity, toxicity
8 Curcumin
1 Celastrol
1 chitosan
1 Artemisinin
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#:1025  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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