Parthenolide / CSCs 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)


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.

Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review
Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy
Can we utilise the circadian clock to target cancer stem cells?


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↑,
5156- PTL,    Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells
- in-vitro, AML, NA
NADPH↑, PPP↑, NRF2↑, ROS↑, CSCs↓, selectivity↑, other↝,
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↓,
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 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 1,   NRF2↑, 1,   OXPHOS↓, 1,   ROS↑, 4,  

Mitochondria & Bioenergetics

MMP↓, 2,  

Core Metabolism/Glycolysis

IDH2↓, 1,   NADPH↑, 1,   PPP↑, 1,   SLC25A1↓, 1,  

Cell Death

Apoptosis↑, 1,   Casp↑, 1,  

Transcription & Epigenetics

other↝, 1,  

DNA Damage & Repair

P53↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

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

Migration

LEF1↓, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↑, 1,   eff↓, 1,   eff↑, 1,   selectivity↑, 2,  
Total Targets: 26

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
4 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#:795  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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