Database Query Results : Curcumin, , TET1

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


TET1, Ten-Eleven Translocation 1: Click to Expand ⟱
Source:
Type:
TET1 (Ten-Eleven Translocation 1) is a gene that plays a crucial role in DNA demethylation and epigenetic regulation.
-Responsible for cell apoptosis, migration, and invasion.
TET1 is a member of the TET family of enzymes, which convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in DNA. This process is essential for maintaining genome stability, regulating gene expression, and preventing tumorigenesis.
TET1 is often downregulated or mutated, leading to decreased 5-hmC levels and aberrant DNA methylation patterns. This can result in the silencing of tumor suppressor genes and the activation of oncogenes, contributing to cancer development and progression.
-Loss of 5hmC is strongly associated with advanced and higher grade ccRCC.
Scientific Papers found: Click to Expand⟱
442- CUR,  5-FU,    Curcumin may reverse 5-fluorouracil resistance on colonic cancer cells by regulating TET1-NKD-Wnt signal pathway to inhibit the EMT progress
- in-vitro, CRC, HCT116
Apoptosis↑,
TumCP↓,
TumCCA↑, block of G0/G1 phase
TET1↑,
NKD2↑,
Wnt↓,
EMT↓,
Vim↑,
E-cadherin↓,
β-catenin/ZEB1↓,
TCF↓, TCF4
AXIN1↓, Axin

422- CUR,    Curcumin induces re-expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines
- in-vitro, BC, HCC-38 - in-vitro, BC, T47D
BRCA1↑,
TET1↑,
DNMT3A↑, Curcumin downregulates the expression of DNMT1 and upregulates TET1 and DNMT3 in HCC-38 cells
DNMT1↓,
SNCG↓,
miR-29b↓, HCC-38 cells
miR-29b↑, upregulates miR-29b in T47D cells


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Apoptosis↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   DNMT1↓, 1,   DNMT3A↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

AXIN1↓, 1,   EMT↓, 1,   NKD2↑, 1,   TCF↓, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   miR-29b↓, 1,   miR-29b↑, 1,   TET1↑, 2,   TumCP↓, 1,   Vim↑, 1,   β-catenin/ZEB1↓, 1,  

Protein Aggregation ⓘ

SNCG↓, 1,  

Clinical Biomarkers ⓘ

BRCA1↑, 1,  
Total Targets: 19

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TET1, Ten-Eleven Translocation 1
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#:657  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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