Database Query Results : Luteolin, , DNMT3A

LT, Luteolin: Click to Expand ⟱
Features:
Luteolin a Flavonoid found in celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers.
-MDR1 expression, MMP-9, IGF-1 and Epithelial to mesenchymal transition.

-Note half-life 2–3 hours
BioAv low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
Pathways:
- induce ROS production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Luteolin — Cancer vs Normal Cell Effects
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR signaling ↔ adaptive suppression Driver Loss of survival and growth signaling Luteolin consistently suppresses PI3K/AKT signaling, explaining growth inhibition and apoptosis sensitization
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of inflammatory survival transcription NF-κB inhibition is a core, repeatedly observed luteolin effect
3 Reactive oxygen species (ROS) ↑ ROS (context- & dose-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Luteolin can act as a pro-oxidant in cancer cells while remaining antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of intrinsic apoptosis Mitochondrial apoptosis follows signaling and redox stress
5 STAT3 signaling ↓ STAT3 activation ↔ minimal Secondary Loss of proliferative and stemness signaling STAT3 suppression contributes to reduced invasion and CSC traits
6 Cell cycle regulation ↑ G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream pathway inhibition
7 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT and protease activity limit invasiveness


DNMT3A, DNA (cytosine-5-)-methyltransferase 3 alpha: Click to Expand ⟱
Source: CGL-Driver Genes
Type: Oncogene
DNA (cytosine-5-)-methyltransferase 3 alpha, commonly referred to as DNMT3A, is an enzyme that plays a crucial role in the process of DNA methylation, which is an important mechanism for regulating gene expression and maintaining genomic stability.
The expression levels of DNMT3A and the presence of mutations can serve as prognostic markers in certain cancers.
In some cancers, DNMT3A is overexpressed, leading to increased DNA methylation of tumor suppressor genes.
Biological Consequences of DNMT3A Loss
-Epigenetic drift rather than uniform hypomethylation
-Persistence of stem-like transcriptional programs
-Increased self-renewal of hematopoietic stem cells
-Impaired differentiation with preserved viability

Importantly, DNMT3A loss does not strongly increase proliferation on its own—it increases clonal persistence and evolutionary potential.


Scientific Papers found: Click to Expand⟱
2915- LT,    Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells
- in-vitro, Colon, HT29 - in-vitro, CRC, SNU-407 - in-vitro, Nor, FHC
DNMTs↓, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases,
TET1↑,
NRF2↑, luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2
HDAC↓, Recently, Zao et al. demonstrated that luteolin epigenetically activates the Nrf2 pathway by downregulating DNA methyltransferase (DNMT) and histone deacetylase (HDAC) expression
tumCV↓, Luteolin decreased the viability of all three cell lines in a dose-dependent manner
BAX↑, luteolin upregulated the expression of the apoptotic protein Bax, active caspase-9, and active caspase-3, while it downregulated the expression of the anti-apoptotic protein Bcl-2,
Casp9↑,
Casp3↑,
Bcl-2↓,
ROS↓, Luteolin promotes ROS scavenging by inducing the expression of antioxidant enzymes
GSS↑, luteolin increased the protein expression of the antioxidant enzymes GCLc, GSS, catalase, and HO-1 in a dose- and time-dependent manner
Catalase↑,
HO-1↑,
DNMT1↓, Luteolin markedly decreased the protein expression of DNMT1, DNMT3A, and DNMT3B in a dose- and time-dependent manner
DNMT3A↓,
TET1↑, In contrast, it markedly increased the protein expression of TET1, TET2, and TET3 in a dose- and time-dependent manner
TET3↑,
TET2↓,
P53↑, Luteolin upregulated the expression of p53 and its target p21 in a dose- and time-dependent manner
P21↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GSS↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Cell Death ⓘ

BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,  

Transcription & Epigenetics ⓘ

TET3↑, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1,  

Migration ⓘ

TET1↑, 2,  

Drug Metabolism & Resistance ⓘ

TET2↓, 1,  
Total Targets: 19

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: DNMT3A, DNA (cytosine-5-)-methyltransferase 3 alpha
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#:118  Target#:86  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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