Parthenolide / GPx1 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)

GPx1, Glutathione Peroxidase: Click to Expand ⟱

Source:

Type:

Widely and abundantly expressed antioxidant enzyme
Glutathione peroxidase (GPx) is an important antioxidant enzyme that plays a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. It utilizes glutathione, a tripeptide composed of glutamine, cysteine, and glycine, as a substrate to carry GPx is part of the body's antioxidant defense system. By reducing oxidative stress, GPx may help prevent the initiation and progression of cancer. Some studies suggest that higher levels of GPx activity are associated with a lower risk of certain cancers.
The tumor microenvironment is often characterized by increased oxidative stress. GPx can influence the behavior of cancer cells and their interactions with surrounding cells. In some cases, cancer cells may upregulate GPx to survive in this oxidative environment, which can contribute to tumor growth and resistance Inhibiting GPx in certain cancer types may sensitize tumor cells to chemotherapy and radiation therapy by increasing oxidative stress.to therapy.

GPX1 is widely expressed in various tissues and is particularly important in maintaining cellular redox balance. GPX1 expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.

Scientific Papers found: Click to Expand⟱

1988-

PTL,

Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies

in-vitro,

lymphoma,

NCI-H929

0.1 µM and 100 µM

(IC50) ranging between 1 µM and 10 µM.

NF-kB↓, ROS↑, GSH↓, MMP↓, GPx1↓,

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 ⓘ

GPx1↓, 1, GSH↓, 1, ROS↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,
Total Targets: 5

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: GPx1, Glutathione Peroxidase

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