Parthenolide / IDH2 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)


IDH2, isocitrate dehydrogenase 2 (NADP+), mitochondrial: Click to Expand ⟱
Source: CGL-Driver Genes
Type: Oncogene
An enzyme that plays a crucial role in the citric acid cycle (Krebs cycle), which is essential for cellular metabolism. Mutations in the IDH2 gene have been implicated in various types of cancer, particularly in hematological malignancies such as acute myeloid leukemia (AML) and certain brain tumors like gliomas.
IDH2 mutations often lead to a gain of function, resulting in the production of 2-hydroxyglutarate (2-HG), an oncometabolite. Elevated levels of 2-HG can disrupt normal cellular processes, including DNA and histone methylation, leading to altered gene expression and promoting tumorigenesis.

IDH2 (Isocitrate Dehydrogenase 2) is another enzyme involved in cellular metabolism, similar to IDH1. It is primarily located in the mitochondria and plays a role in the citric acid cycle. Mutations in the IDH2 gene are associated with various cancers, particularly acute myeloid leukemia (AML) and some solid tumors.


Scientific Papers found: Click to Expand⟱
1991- PTL,    A novel SLC25A1 inhibitor, parthenolide, suppresses the growth and stemness of liver cancer stem cells with metabolic vulnerability
- in-vitro, Liver, HUH7
TumCCA↑, Apoptosis↑, CSCs↓, ROS↑, OXPHOS↓, MMP↓, SLC25A1↓, IDH2↓,

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 ⓘ

OXPHOS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

IDH2↓, 1,   SLC25A1↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,  
Total Targets: 8

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: IDH2, isocitrate dehydrogenase 2 (NADP+), mitochondrial
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#:153  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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