Pin1 Cancer Research Results

Pin1, Peptidyl-prolyl cis-trans isomerase, NIMA-interacting 1: Click to Expand ⟱
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Type:
Pin1 (Peptidyl-prolyl cis-trans isomerase, NIMA-interacting 1) is a peptidyl-prolyl isomerase that specifically recognizes phosphorylated serine/threonine-proline motifs, thereby modulating the conformation and function of various proteins. This post-phosphorylation regulation can directly affect cell division, survival, and metastasis—all of which impact cancer progression.

High Pin1 expression in breast, pca, had and lung cancers is associated with more aggressive tumor behavior, increased metastatic potential, and poorer overall survival.

Inhibitors:
-Juglone (5-hydroxy-1,4-naphthoquinone) is one of the most widely studied natural inhibitors of Pin1.
-All‑trans Retinoic Acid (ATRA).
A metabolite of vitamin A, ATRA has been reported to inhibit Pin1 activity.
-EGCG
-Curcumin (Proposed)

Juglone is thought to act via direct covalent modifications of Pin1, whereas ATRA and EGCG likely interact through non-covalent binding.
Scientific Papers found: Click to Expand⟱
5113- JG,    Juglone in Oxidative Stress and Cell Signaling
- Review, Var, NA - Review, AD, NA
ROS↑, However, being a quinone molecule, juglone could also act as a redox cycling agent and produce reactive oxygen species.
Pin1↓, Notably, juglone is an inhibitor of Pin1 (peptidyl-prolyl cis/trans isomerase) that could regulate phosphorylation of Tau, implicating potential effects of juglone in Alzheimer’s disease.
antiOx⇅, Juglone may have either pro- or antioxidant characteristics depending on the concentrations
*ROS↓, A recent study in a transgenic mouse model of Alzheimer’s disease demonstrated that the walnut supplementation can reduce oxidative damage
SMAD2↓, juglone reduces oxidative stress by inhibiting the phosphorylation of Smad2 in the kidney
GSH↓, cytotoxicity of juglone is due to two different mechanisms, namely, redox cycling and the reaction with glutathione (GSH) . toxicity of juglone is the formation of adducts, which also causes the glutathione depletion.
lipid-P↑, Juglone enhances lipid peroxidation predominantly through redox cycling
TumCCA↓, Figure3
BAX↑,
Bcl-2↓,
Casp3↑,
Casp9↑,
Ca+2↑,
Cyt‑c↑,
AntiFungal↑, Juglone may be as effective as commercially available antifungal agents including zinc undecylenate and selenium sulfide
Bacteria↓, Juglone has been shown to possess antibacterial activities
Akt↓, juglone has been shown to suppress the Akt pathway

5115- JG,    Natural Products to Fight Cancer: A Focus on Juglans regia
- Review, Var, NA
Casp3↑, In LNCaP cells, it triggered apoptosis through the intrinsic pathway, promoting the activation of caspases 3 and 9, and decreasing mitochondrial potential (ΔΨ)
Casp9↑,
MMP↓,
AR↓, At sub-toxic concentrations, it downregulated ARs and PSA expression
PSA↓,
E-cadherin↑, Juglone upregulated the expression of the epithelial marker E-cadherin while reducing the mesenchymal factors N-caderin and vimentin.
N-cadherin↓,
Vim↓,
Akt↓, Furthermore, it synergistically inhibited the Akt/glycogen synthase kinase-3β (GSK-3β)/Snail axis that would physiologically promote E-cadherin repression and EMT induction
GSK‐3β↓,
EMT↑,
TumCI↓, decreased cell invasions by 56% and 80%, respectively, on BxPC-3 and PANC-1 cell lines.
MMP9↓, Juglone significantly dropped the protein level of MMP-9 and the vascular endothelial growth factor (VEGF) reporter Phactr-1 in both cell lines, while a drop of MMP-2 was evident only on BxPC-3
VEGF↓,
MMP2↓,
TumCCA↑, juglone promoted G1 cell-cycle arrest [94,95] and ROS-driven apoptosis
ROS↑,
Apoptosis↑,
GSH↓, Glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase protein levels diminished
Catalase↓,
SOD↓,
GPx↓,
DNAdam↑, juglone cytotoxicity is, at least partially, ascribed to DNA damage
γH2AX↑, high levels of γ-H2AX were registered when juglone was tested in combination with ascorbate.
eff↑, juglone’s anticancer profile (in terms of proliferation inhibition, cytotoxicity, and ROS induction) was highly improved by ascorbate [115], revealing an interesting synergistic activity between these two compounds
BAX↑, upregulation of many proteins involved in the intrinsic and extrinsic pathway, such as Bax, Cyt-c, Fas cell surface death receptor (Fas), Fas-ligand.
Fas↑,
Pin1↓, On U251 glioblastoma cells, juglone arrested cell growth by promoting apoptosis with the involvement of peptidyl-prolyl cis/trans isomerase (Pin1) inhibition [111]. Juglone is a well-known Pin1 inhibitor


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   Catalase↓, 1,   GPx↓, 1,   GSH↓, 2,   lipid-P↑, 1,   ROS↑, 2,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 1,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   Fas↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   GSK‐3β↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   SMAD2↓, 1,   TumCI↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

Pin1↓, 2,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   Bacteria↓, 1,  
Total Targets: 39

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Pin1, Peptidyl-prolyl cis-trans isomerase, NIMA-interacting 1
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

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