Database Query Results : Parthenolide, ,

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)


Scientific Papers found: Click to Expand⟱
1992- PTL,    Parthenolide induces ROS-dependent cell death in human gastric cancer cell
- in-vitro, BC, MGC803
TumCCA↑, Casp↑, Apoptosis↑, Necroptosis↑, RIP1↓, RIP3↑, MLKL↑, ROS↑, eff↓,
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↝,
5155- PTL,    Parthenolide Inhibits STAT3 Signaling by Covalently Targeting Janus Kinases
- in-vitro, Liver, HepG2 - in-vitro, Nor, MEF - in-vitro, Cerv, HeLa - in-vitro, BC, MDA-MB-453
JAK↓, ROS↑, TumCMig↓, TumCG↓, STAT3↓,
5154- PTL,    Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro
- in-vitro, Melanoma, NA
tumCV↓, MMP↓, Casp3↑, Thiols↝,
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↓,
1996- PTL,    Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells
- in-vitro, CRC, COLO205
Apoptosis↑, GSH↓, ROS↑, Ca+2↑, GRP78/BiP↑, ER Stress↑, eff↓, eff↑, Thiols↓,
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↓,
1994- PTL,    Parthenolide Inhibits Tumor Cell Growth and Metastasis in Melanoma A2058 Cells
- in-vitro, Melanoma, A2058 - in-vitro, Nor, L929
tumCV↓, selectivity?, ROS?, BAX↑, TumCCA?, MMP2↓, MMP9↓, TumCMig↓, eff↑,
1993- PTL,    Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer
- in-vitro, Cerv, HeLa
tumCV↓, TumAuto↑, Casp3↑, BAX↑, Beclin-1↑, ATG3↑, ATG5↑, Bcl-2↓, mTOR↓, PI3K↓, Akt↓, PTEN↑, ROS↑, MMP↓,
1983- PTL,    Targeting thioredoxin reductase by micheliolide contributes to radiosensitizing and inducing apoptosis of HeLa cells
- in-vitro, Cerv, HeLa
eff↑, TrxR↓, ROS↑, RadioS↑,
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↓,
1990- PTL,    Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway
- in-vitro, AD, PC12
*Apoptosis↓, *ROS↓, *MMP↓, *memory↑, *eff↑,
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↓,
1987- PTL,  Rad,    A NADPH oxidase dependent redox signaling pathway mediates the selective radiosensitization effect of parthenolide in prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Nor, PrEC
selectivity↑, RadioS↑, ROS↑, *ROS∅, NADPH↑, Trx↓, PI3K↑, Akt↑, p‑FOXO3↓, SOD2↓, Catalase↓, radioP↑, *NADPH∅, *GSH↑, *GSH/GSSG↑, *NRF2↑,
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↓,
1984- PTL,    Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells
- in-vitro, Cerv, HeLa
AntiCan↑, TrxR1↓, TrxR2↓, ROS↑, Apoptosis↑, eff↓, eff↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 19

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   GPx1↓, 1,   GSH↓, 3,   ox-Keap1↓, 1,   rd-Keap1↑, 1,   NRF2↑, 1,   NRF2∅, 1,   OXPHOS↓, 1,   ROS?, 1,   ROS↑, 14,   SOD2↓, 1,   Thiols↓, 1,   Thiols↝, 1,   Trx↓, 3,   TrxR↓, 1,   TrxR1↓, 1,   TrxR2↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 5,  

Core Metabolism/Glycolysis ⓘ

IDH2↓, 1,   NADPH↑, 3,   PPP↑, 1,   SLC25A1↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 1,   Apoptosis↑, 4,   BAX↑, 2,   Bcl-2↓, 1,   Casp↑, 2,   Casp3↑, 2,   JNK↑, 1,   MLKL↑, 1,   Necroptosis↑, 1,   RIP1↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   ATG5↑, 1,   Beclin-1↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA?, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 4,   p‑FOXO3↓, 1,   mTOR↓, 1,   PI3K↓, 1,   PI3K↑, 1,   PTEN↑, 1,   STAT↓, 1,   STAT3↓, 1,   TCF-4↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

Ca+2↑, 1,   LEF1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   RIP3↑, 1,   TumCMig↓, 2,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   JAK↓, 1,   NF-kB↓, 6,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   eff↓, 5,   eff↑, 5,   RadioS↑, 3,   selectivity?, 1,   selectivity↑, 3,  

Functional Outcomes ⓘ

AntiCan↑, 1,   radioP↑, 2,  
Total Targets: 73

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

GSH↑, 1,   GSH/GSSG↑, 1,   ox-Keap1↑, 1,   NRF2↑, 2,   ROS↓, 2,   ROS∅, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH∅, 1,  

Cell Death ⓘ

Apoptosis↓, 2,   BAX↓, 1,  

DNA Damage & Repair ⓘ

P53↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,   p‑NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Functional Outcomes ⓘ

memory↑, 1,  
Total Targets: 15

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#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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