Parthenolide / TCF-4 Cancer Research Results

PTL, Parthenolide: Click to Expand ⟱
Features:
Parthenolide is a naturally occurring sesquiterpene lactone derived from the medicinal plant feverfew (Tanacetum parthenium).
-Micheliolide (MCL) is converted readily from parthenolide (PTL), and has better stability and solubility than PTL
-Parthenolide is a natural compound used to treat migraines and arthritis and found to act as a potent NF-κB signaling inhibitor.

Main activities include:
-Inhibition of NF-κB Signaling:
-Induction of Oxidative Stress (ROS): oxidative stress can overwhelm the antioxidant defenses of the cancer cells, leading to cellular damage and death
-Parthenolide can interfere with STAT3 signaling, inhibiting the transcription of genes that favor tumor growth and resistance to apoptosis.
-Modulation of the MAPK/ERK Pathway:
-Impact on the JNK Pathway:
-Parthenolide has been shown to target cancer stem cells

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 NF-κB DNA-binding (p65/RelA Cys38 alkylation) ↓ NF-κB DNA binding Suppresses pro-survival transcription Direct mechanism: parthenolide inhibits NF-κB most likely by alkylating p65 at Cys38, reducing DNA binding (ref)
2 Thioredoxin reductase (TrxR1 / TrxR2) ↓ TrxR activity Redox buffering collapse Parthenolide directly targets TrxR1/TrxR2 (selenocysteine-containing enzymes) and inhibits function (ref)
3 ROS accumulation (superoxide / oxidative stress) ↑ ROS Upstream cytotoxic trigger Same TrxR-targeting study shows TrxR inhibition shifts redox state and drives ROS accumulation leading to apoptosis (ref)
4 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Mitochondrial dysfunction Parthenolide increases ROS and is reported with a combined ΔΨm reduction accompanying apoptosis across cancer cell lines (ref)
5 Intrinsic apoptosis (caspase-3 activation) ↑ caspase-3 Programmed cell death Parthenolide treatment associated with mitochondrial membrane depolarization and caspase-3 activation in cancer cells (ref)
6 STAT3 signaling (via JAK2 covalent inhibition) ↓ STAT3 phosphorylation/signaling Reduced survival / migration programs Parthenolide covalently modifies JAK2 cysteines, suppressing kinase activity and inhibiting STAT3 signaling (ref)
7 AML stem cell targeting (LSC vulnerability; regimen context) ↓ AML stem cell survival Stem/progenitor depletion Parthenolide-based regimen (parthenolide + 2DG + temsirolimus) demonstrates potent targeting of AML stem cells (ref)
8 In vivo anti-tumor effect (xenograft; parthenolide analog evidence) ↓ tumor growth Demonstrated efficacy (derivative) Note: this is for an orally bioavailable parthenolide analog (DMAPT), not native parthenolide (ref)


TCF-4, Transcription Factor 4: Click to Expand ⟱
Source:
Type:
TCF4 gene (Transcription Factor 4) is a transcription factor that plays a crucial role in the Wnt/β-catenin signaling pathway, which is involved in cell proliferation, differentiation, and survival.
TCF4 gene has been found to be:
     Amplified in 15% of breast cancer cases
     Mutated in 10% of lung cancer cases
     Deleted in 20% of prostate cancer cases
     Methylated in 30% of colorectal cancer cases
Scientific Papers found: Click to Expand⟱
1989- PTL,    Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties
- Review, Var, NA
eff↑, NF-kB↓, STAT↓, ROS↑, Inflam↓, Wnt↓, TCF-4↓, LEF1↓, GSH↓, MMP↓, Casp↑, eff↓, CSCs↓,

Showing Research Papers: 1 to 1 of 1

* 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 ⓘ

GSH↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Casp↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   STAT↓, 1,   TCF-4↓, 1,   Wnt↓, 1,  

Migration ⓘ

LEF1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,   eff↑, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TCF-4, Transcription Factor 4
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#:8  Target#:967  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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