PP2A Cancer Research Results

PP2A, serine/threonine phosphatase: Click to Expand ⟱
Source:
Type:
Protein Phosphatase 2A (PP2A) plays a critical role in Alzheimer’s disease (AD), especially in relation to tau pathology.
-PP2A dephosphorylates tau, thus reducing its toxicity.
-MID1 Negatively Regulates PP2A
-In AD, PP2A activity is decreased, leading to accumulation of hyperphosphorylated tau.
-Amyloid-β (Aβ) peptides may inhibit PP2A, indirectly promoting tau pathology.
-Aβ and tau pathologies are interconnected, and PP2A sits at a crossroads of both.

Some natural products that might upregulate PP2A:
-resveratrol
-Sodium selenate
-Berberine
-Fisetin
-Metformin (via indirect mechanisms)
Scientific Papers found: Click to Expand⟱
4298- BBR,    Berberine mitigates cognitive decline in an Alzheimer’s Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
- in-vivo, AD, NA
*cognitive↑, Berberine could improve 3×Tg AD mice’s cognitive function
*p‑tau↓, Berberine could attenuate the hyperphosphorylation of tau
*GSK‐3β↓, attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A
*PP2A↑, inhibition of GSK3β or activation of PP2A attenuates tau hyperphosphorylation, thus, ameliorates cognitive impairment
*memory↑, Berberine-treated mice showed better performance in spatial learning and memory test
*Akt↑, Berberine decreases tau phosphorylation via activation of Akt and inhibition of GSK3β
*LC3II↑, both LC3-Ⅱ and Beclin-1 in the hippocampus of BBR-treated group were dramatically increased compared with the 3×Tg AD mice
*Beclin-1↑,

6650- Cen,    Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review
- Review, AD, NA
*BioAv↝, madecassoside, asiaticoside, madecassic acid, and asiatic acid are widely distributed in the body and madecassoside, asiaticoside may exert their biological activity through converted into aglycone (madecassic acid, and asiatic acid).
*BioAv↝, C. asiatica enhances the function of the nervous system. It dissolves in methanol, ethanol, and water.
*MDA↓, Male Wistar rats – MDA ↓, GSH ↑, SOD ↑, AChE↓
*GSH↑,
*SOD↑,
*AChE↓,
*memory↑, Male SD rats; hippocampal cell – Spatial working memory↑, Ki-67 cells↑
*Ki-67↑,
*Catalase↑, Male SD rats MAPK SOD↑, LPO↑, CAT↑, GSH↑, dopamine↑, glutamate↑, Syn1↑, Stx1A↑, PI3K↑, PDK1↑, PEBP↓, VMAT2↑, TH ↑, MAPK ↑, BDNF↑, NGF↑
*PI3K↑,
*BDNF↑,
*NGF↑,
*ROS↓, Water extract of CA Tg2576 mice – ROS↓, NRF2↑, GCLC↑, HMOX1↑, NQO1↑, ATP↑, Mt-ND1↑, Mt-ATP6↑, Mt-CO1↑, Mt-CYB↑, oxygen consumption rate↑
*NRF2↑,
*HO-1↑,
*NQO1↑,
*ATP↑,
*OCR↑,
*TNF-α↓, Ethanolic extract of CA Male SD rats – TNF-α↓, BDNF↑
*PP2A↑, Ethanolic extract of CA Male albino Wistar rats PP2A/GSK-3B PP2A↑, GSK-3B↓, Bcl-2↑
*GSK‐3β↓,
*Bcl-2↑,
*TrkB↑, Standardized extract of CA Male Wistar rats – NR2A↑, NR2B↑, BDNF↑,TrkB↑
*NOTCH1↑, Asiatic acid Male SD rats – Notch1↑, SOX2↑, DCX↑, Nrf2↑, nestin↑, p21 positive cells↓, MDA↓
*SOX2↑,
*Nestin↑,
*MDA↓,
*MAOA↓, Asiaticoside-D Worms – MAO-A↓, MAO-B↓
*MAOB↓,
*GPx↑, Previous studies found that C. asiatica and its triterpenoids could effectively increase SOD and GPX activities, activate nuclear factor erythroid-2-related factor 2, improve the cognitive impairment of animals,
*cognitive↑,
*ROS↓, C. asiatica and its triterpenoids could reduce ROS production
*neuroP↑, they reduced related nerve cell apoptosis, increased synaptic density, and improved the survival rate of neural cells
*glucose↓, Methanol extract of CA Male SD rats – Blood glucose ↓, food and water intake ↓, ALT↓, AST↓, PFK ↑, GS ↑, GP↑, glycogen content ↑
*ALAT↓,
*AST↓,
*PFK↓,
*Weight↓, inhibit weight gain
*Inflam↓, (4) ameliorate inflammation,
*AntiDiabetic↑, C. asiatica extract and related components (asiatic acid, madecassoside) for the treatment of endocrine diseases such as diabetes, obesity and osteoporosis are excellent.
*Obesity↓,
*Wound Healing↑, The C. asiatica extract and its triterpenoids had certain therapeutic and relieving effects on acne, baldness, vitiligo, atopic dermatitis, and wounds. C. asiatica extract can effectively promote wound healing in diabetic patients
*cardioP↑, C. asiatica has a positive effect on cardiovascular diseases.
*GutMicro↑, C. asiatica and its triterpenoids also have therapeutic effects on digestive disorders, which is mainly reflected by improved liver fibrosis, colitis, and gastric mucosal damage; and even reduced Helicobacter pylori gastric colonization
*Sepsis↓, Asiatic acid can improve the side effects caused by antibiotics, reverse multidrug resistance (MDR), and reduce sepsis.
*BioAv↑, C. asiatica cream containing 5.12% asiaticoside and 5.1% madecassoside can be completely absorbed by the skin and effectively improve pigmentation and may be used in treating hypertrophic scars

6818- EMD,    Emodin Rescued Hyperhomocysteinemia-Induced Dementia and Alzheimer's Disease-Like Features in Rats
- in-vivo, AD, NA
*Aβ↓, emodin (especially 80 mg/kg/d) reduced the levels of β-amyloid and tau phosphorylation, decreased the levels of β-site amyloid precursor protein-cleaving enzyme 1, and improved the activity of protein phosphatase 2A.
*p‑tau↓,
*PP2A↑,
*cAMP↑, hippocampi of HCY-E40 and HCY-E80 rats, the neuron numbers, levels of synaptic proteins, and phosphorylation of the cAMP responsive element-binding protein at Ser133 were increased
*5LO↓, In addition, depressed microglial activation and reduced levels of 5-lipoxygenase, interleukin-6, and tumor necrosis factor α were also observed.
*IL6↓,
*TNF-α↓,
*ROS↓, Lastly, hyperhomocysteinemia-induced microangiopathic alterations, oxidative stress, and elevated DNA methyltransferases 1 and 3β were rescued by emodin.
*DNMT1↓,

6826- EMD,    Exploring the therapeutic potential of natural compounds for Alzheimer's disease: Mechanisms of action and pharmacological properties
*AntiCan↑, Emodin has a wide range of pharmacological activities, including anticancer, hepatoprotective, anti-inflammatory, antioxidant, and antibacterial activities
*hepatoP↑,
*Inflam↓,
*antiOx↑,
*Bacteria↓,
*Aβ↓, Although Emodin did not reduce plasma homocysteine levels, it reduced Aβ and tau phosphorylation levels, decreased levels of β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and increased protein phosphatase 2 A (PP2A) activity.
*p‑tau↓,
*BACE↓,
*PP2A↑,

4302- Gins,    Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease
- Review, AD, NA
*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape

4289- RES,    Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells
- in-vitro, AD, NA
*antiOx↑, Resveratrol (Res), as a polyphenol anti-oxidant, has been considered to have therapeutic potential for the treatment of AD.
*p‑tau↓, Res significantly decreased FA-induced cytotoxicity, reduced cell apoptosis rates, and inhibited the hyperphosphorylation of tau protein at Thr181 in a dose-dependent manner.
*GSK‐3β↓, Further tests revealed that this effect was associated with the suppression of glycogen synthase kinase (GSK-3β)
*CaMKII ↓, and calmodulin-dependent protein kinase II (CaMKII) activities, both of which are important kinases for tau protein hyperphosphorylation.
*PP2A↑, Res was found to increase the activity of phosphoseryl/phosphothreonyl protein phosphatase-2A (PP2A).
*neuroP↑, Neuroprotective effects of Res against FA-induced cytotoxicity

4288- RES,    Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β
- in-vivo, AD, NA
*memory↑, RES improved both short and long-term memory as analyzed by novel object recognition task and significantly increased brain levels of glutathione in both control and CdCl2-treated rats.
*GSH↑,
*ROS↓, It also inhibited ROS levels of malondialdehyde in the brains of CdCl2-treated rats.
*MDA↓,
*p‑tau↓, RES decreased the phosphorylation rate of Tau at Ser199 and Ser296.
*PI3K↑, RES activated PI3K/Akt signaling pathway in both control and CdCl2 treated rats by increasing levels of p-PI3K (Tyr607) and p-Akt (Ser473)
*Akt↑,
*AMPK↑, significant increase in the levels of AMPK and p-AMPK, known upstream regulators of PI3K/Akt signaling pathway.
*PP2A↑, RES inhibits Tau phosphorylation in rat’s brain by activating PP2A protein and AMPK/PI3K/Akt-induced inhibition of GSK3β.
*GSK‐3β↓,

4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented
*Inflam↓, Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol contained in red wine, peanuts, and some berries, is known for its anti-atherosclerotic, anti-inflammatory, antioxidant, and longevity-promoting properties
*antiOx↑,
*GSH↑, ↑glutathione in brain
*HO-1↑, ↑HO-1 ↓iNOS in hippocampus
*iNOS↓,
*BDNF↑, ↑BDNF, ↑pCREB, ↑PKA, ↑BCl-2 expression, ↓BAX expression, ↓IL-1β, IL-6, in hippocampus
*p‑CREB↑,
*PKA↑,
*Bcl-2↑,
*BAX↓,
*IL1β↓,
*IL6↓,
*MMP9↓, ↓MMP-9 in cerebrospinal fluid
*memory↑, ↑memory performance
*AMPK↑, ↑AMPK, ↑PGC-1, ↓NF-κB / IL-1β / NLRP3 in hippocampus and prefrontal cortex
*PGC-1α↓,
*NF-kB↓,
*Aβ↓, may counteract the formation of neurotoxic Aβ
*SIRT1↑, Resveratrol via SIRT-1 can, therefore, be expected to reduce the level of hyperphosphorylated tau and provide protection against neurodegeneration.
*p‑tau↓,
*PP2A↑, resveratrol by lowering the expression of MID1 ubiquitin ligase increases protein phosphatase 2A (PP2A) activity and promotes tau dephosphorylation by preventing its accumulation
*lipid-P↓, resveratrol abolishes Aβ-induced lipid peroxidation and expression of heme oxygenase-1 (HO-1) reduction;
*NLRP3↓, Researchers achieved a significant reduction in the levels of NF-κB (nuclear factor κ-light-chain enhancer of activated B cell), interleukin 1β and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammation markers
*BACE↓, figure 1

4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, Resveratrol induces dephosphorylation of Tau
*PP2A↑, resveratrol, a polyphenol, significantly induces PP2A activity and reduces Tau phosphorylation at PP2A-dependent epitopes.
*neuroP↑, resveratrol is more and more being established as a neuroprotective drug after ischemic brain injury and in neurodegenerative disorders including Parkinson’s Disease13,14, AD15,16 and Huntington’s Disease
*antiOx↑, resveratrol has anti-oxidant activity19,20, inhibits cycloxygenase activity21,22, ribonucleotide reductase23, protein kinase C24, DNA polymerase 25 and has antiestrogenic properties26,27 and anti-platelet activity
COX2↓,
*AntiAg↑,
*SIRT1↑, it activates Sirt1, an NAD+-dependent protein deacetylase28,29 and also has been demonstrated to activate AMP kinase (AMPK)30,31, an important glucose sensor that inhibits acetyl-CoA carboxylase, thereby increasing oxidation of fatty acids and decre
*AMPK↑,
*Acetyl-CoA↓,
*FAO↑,
*ADAM10↑, Resveratrol has been suggested to induce the α-secretase ADAM10, which outcompetes BACE1 and thereby reduces Aβ-production
*BACE↓,
*Aβ↓,
*memory↑, interestingly, the resveratrol-mediated reduction of Aβ increases life span and improves learning and memory
*Inflam↓, reduces neuroinflammation47 and reduces oxidative stress48.
*ROS↓,


Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics(tgid=3) ⓘ

ETC↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   NADH:NAD↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Myc↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

E2Fs↓, 1,  

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

Diff↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

KRAS↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

HIF-1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   PD-1↓, 1,   PD-L1↓, 1,  

Protein Aggregation(tgid=19) ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

KRAS↓, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 4,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 3,   HO-1↑, 2,   lipid-P↓, 1,   MDA↓, 3,   NQO1↑, 1,   NRF2↑, 2,   ROS↓, 5,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,   OCR↑, 1,   PGC-1α↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Acetyl-CoA↓, 1,   ALAT↓, 1,   AMPK↑, 3,   cAMP↑, 1,   CREB↑, 1,   p‑CREB↑, 1,   FAO↑, 1,   glucose↓, 1,   PFK↓, 1,   PPARγ↓, 1,   SIRT1↑, 2,  

Cell Death(tgid=5) ⓘ

Akt↑, 3,   BAX↓, 1,   Bcl-2↑, 2,   iNOS↓, 1,   MAPK↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

CaMKII ↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNMT1↓, 1,  

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

ERK↑, 1,   GSK‐3β↓, 4,   Nestin↑, 1,   NOTCH1↑, 1,   PI3K↑, 3,   SOX2↑, 1,  

Migration(tgid=13) ⓘ

5LO↓, 1,   AntiAg↑, 1,   APP↓, 1,   Ki-67↑, 1,   MMP9↓, 1,   PKA↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL1β↓, 1,   IL6↓, 2,   Inflam↓, 4,   NF-kB↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,   ADAM10↑, 2,   BDNF↑, 2,   MAOA↓, 1,   NGF↑, 1,   p‑tau↓, 8,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 5,   BACE↓, 4,   IDE↑, 1,   MAOB↓, 1,   NLRP3↓, 1,   PP2A↑, 9,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 2,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   GutMicro↑, 1,   IL6↓, 2,   Ki-67↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   cardioP↑, 1,   cognitive↑, 3,   hepatoP↑, 1,   memory↑, 6,   neuroP↑, 5,   Obesity↓, 1,   Weight↓, 1,   Wound Healing↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,   Sepsis↓, 1,  
Total Targets: 84

Scientific Paper Hit Count for: PP2A, serine/threonine phosphatase
4 Resveratrol
2 Emodin
1 Berberine
1 Centella asiatica / Gotu kola → asiaticoside
1 Ginseng
1 Niclosamide (Niclocide)
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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