Parthenolide / NF-kB 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)


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
5157- PTL,    An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells
- vitro+vivo, AML, NA
CSCs↓, selectivity↑, BioAv↓, BioAv↑, ROS↑, NF-kB↓, P53↑,
5153- PTL,    Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones
- in-vitro, NA, NA
NF-kB↓,
1995- PTL,    The protective effect of parthenolide in an in vitro model of Parkinson's disease through its regulation of nuclear factor-kappa B and oxidative stress
- in-vitro, Park, SH-SY5Y
*Apoptosis↓, *ROS↓, *BAX↓, *NF-kB↓, *P53↓, *p‑NF-kB↓,
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↓,
1988- PTL,    Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies
- in-vitro, lymphoma, NCI-H929
NF-kB↓, ROS↑, GSH↓, MMP↓, GPx1↓,
1986- PTL,    Modulation of Cell Surface Protein Free Thiols: A Potential Novel Mechanism of Action of the Sesquiterpene Lactone Parthenolide
- in-vitro, NA, NA
JNK↑, ROS↑, eff↓, NF-kB↓, Trx↓,
1985- PTL,    KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Nor, PrEC - in-vivo, NA, NA
ROS↑, NADPH↑, RadioS↑, radioP↑, Trx↓, *ox-Keap1↑, ox-Keap1↓, rd-Keap1↑, *NRF2↑, NRF2∅, NF-kB↓,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GPx1↓, 1,   GSH↓, 2,   ox-Keap1↓, 1,   rd-Keap1↑, 1,   NRF2∅, 1,   ROS↑, 5,   Trx↓, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

NADPH↑, 1,  

Cell Death ⓘ

Casp↑, 1,   JNK↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 2,   STAT↓, 1,   TCF-4↓, 1,   Wnt↓, 1,  

Migration ⓘ

LEF1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 6,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   eff↓, 2,   eff↑, 1,   RadioS↑, 1,   selectivity↑, 1,  

Functional Outcomes ⓘ

radioP↑, 1,  
Total Targets: 26

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ox-Keap1↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,  

DNA Damage & Repair ⓘ

P53↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,   p‑NF-kB↓, 1,  
Total Targets: 8

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
7 Parthenolide
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#:214  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page