PAI-1/SERPINE1 Cancer Research Results

PAI-1/SERPINE1, plasminogen activator inhibitor-1: Click to Expand ⟱
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PAI-1 (plasminogen activator inhibitor-1; SERPINE1) is a secreted serine-protease inhibitor that primarily inhibits tissue-type and urokinase-type plasminogen activators (tPA/PLAT and uPA/PLAU), thereby regulating plasmin generation, fibrinolysis and extracellular-matrix remodeling. In many cancers, PAI-1 is overexpressed by tumour cells and stromal cells and can promote tumour-cell survival, migration, invasion, angiogenesis, epithelial–mesenchymal transition, metastasis and resistance to therapy through both protease-dependent and signalling functions involving interactions with vitronectin, integrins and LRP1. High tumour or circulating PAI-1 is associated with poor prognosis in several malignancies, particularly breast cancer. The typical cancer-associated direction is therefore generally up, while the desired anticancer modulation is commonly down or functional inhibition. PAI-1 is also strongly associated with cellular senescence and is frequently used as a component of the senescence-associated secretory phenotype (SASP), although elevated PAI-1 alone is not sufficient to establish cellular senescence. PAI-1 is kept separate from PAI-2/SERPINB2 and from its upstream plasminogen activators uPA and tPA.

In cancer, PAI-1 is commonly upregulated and is associated with invasion, angiogenesis, metastasis, treatment resistance, and poor prognosis, although its biology is context-dependent.
Scientific Papers found: Click to Expand⟱
7224- GAs,    Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity
- in-vitro, BC, MCF7 - in-vitro, BC, MDA-MB-231
Wound Healing↓, All seven GA and their mixture inhibited wound healing in MCF-7 and MDA-MB 231 breast cancer cells.
uPA↓, mixture showed a significant down-regulation of urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9).
PAI-1/SERPINE1↓,
CXCR4↓,
MMP9↓,
TumCMig↓, GA revealed considerable anti-migratory activity at non-cytotoxic concentrations, indicating anti-metastatic activity with low toxicity.
NF-kB↓, effect can be explained by the inhibition of NEMO sumoylation leading to inhibition of IκBα degradation and consequently a reduction of NF-κB activity

7567- HYP,    Hyperoside: A review on its sources, biological activities, and molecular mechanisms
- Review, Var, NA
*AntiCan↑, anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects.
*Bacteria↓,
*AntiViral↑,
*antiD↓,
*RenoP↑, Kidney protection
*hepatoP↑, Liver protection
*eff↑, treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers.
*Sepsis↓,
*AntiArt↑,
*Stroke↓,
TumCMig↓, hyperoside has been shown to inhibit the migration and invasion properties of A549 cells by suppressing the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase-2 inhibitor (TIMP-2), matrix metalloproteinase (MMP)-2
TumCI↓,
MTA1↓,
TIMP2↓,
MMP2↓,
MMP↓, disrupted the penetration of the mitochondrial membrane, and triggered mitochondrial cytochrome C and apoptosis inducers into the cytoplasm
Cyt‑c↑,
Akt↓, inhibited the Akt/mTOR/p70S6K signaling pathway in NSCLC cells to promote autophagy and exerted anticancer activity
mTOR↓,
P70S6K↓,
TumAuto↑,
PD-L1↓, thereby inhibiting PD-L1 expression at the transcriptional leve
TNF-α↓, subsequently, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1b, IL-6 and IL-8, were significantly down-regulated
IL1β↓,
IL6↓,
IL8↓,
Bcl-2↓, Hyperoside was reported to inhibit the over-expression of B-cell lymphoma factor 2 (Bcl)-2 and Bcl-x in lung cancer cells, and up-regulate the preapoptotic factors such as Bax, Bad, and Bak.
Bcl-xL↓,
BAX↑,
BAD↑,
Bak↑,
VEGF↓, decreasing the HeLa cell's vascular endothelial growth factor (VEGF) expression levels in HeLa cells.
Casp3↑, hyperoside promoted apoptosis via enhancing caspase-3 and caspase-8 protein expression, and on the other hand, by promoting tumor suppressor gene P35 expression
Casp8↑,
P53↑,
GSH↓, Hyperoside could also reduce glutathione levels in HeLa cells, superoxide dismutase (SOD), and Catalase (CAT) viability.
SOD↓,
Catalase↓,
TAC↓, reduced the antioxidant capacity and thus to inhibit cancer cell growth
XIAP↓, MCF-7 and 4 T1 cells Decreased the levels of Bcl-2 and XIAP; increased the levels of Bax and cleaved cysteine protease-3; decreased the production of ROS and inhibited NFκB signal pathway
ROS↓,
NF-kB↓,
TLR4↓, MDA-MB-231 cells Inhibited TLR4-NF-κB signaling pathways; decreased the expression of Bcl-2; enhanced the expression of pro-apoptotic Bax and the level of pro-inflammatory cytokine IL-6
P-gp/ABCB1↓, S180 cancer cell Reduced the expression of P-gp, LRP and Bcl-2 and increased the expression of Fas; inhibited bad phosphorylation and increased p27 level
LRP1↓,
Fas↑,
p27/CDKN1B↑,
*cardioP↑, Cardiovascular protection In vivo pulmonary embolism and arterial thrombosis model Prolonged the activated prothrombin time and suppressed thrombin and FXa activities; inhibit the production of PAI-1 induced by TNF-α
*AntiThr↑,
*PAI-1/SERPINE1↓,
*BUN↓, Reduced the contents of serum angiotensin converting enzyme ArgII, ALD, U-mAlb, BUN, SCR, ALT, and AST
*ALAT↓,
*AST↓,
*neuroP?, Neuroprotection


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:


NA, unassigned(tgid=0) ⓘ

MTA1↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GSH↓, 1,   ROS↓, 1,   SOD↓, 1,   TAC↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,   XIAP↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   BAD↑, 1,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   Fas↑, 1,   p27/CDKN1B↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

mTOR↓, 1,   P70S6K↓, 1,  

Migration(tgid=13) ⓘ

LRP1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   PAI-1/SERPINE1↓, 1,   TIMP2↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   uPA↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 2,   PD-L1↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

Wound Healing↓, 1,  
Total Targets: 44

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1,   antiD↓, 1,   Stroke↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   BUN↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1,  

Migration(tgid=13) ⓘ

PAI-1/SERPINE1↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 1,   hepatoP↑, 1,   neuroP?, 1,   RenoP↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1,   Bacteria↓, 1,   Sepsis↓, 1,  
Total Targets: 18

Scientific Paper Hit Count for: PAI-1/SERPINE1, plasminogen activator inhibitor-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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