PDE4 Cancer Research Results

PDE4, Phosphodiesterase 4: Click to Expand ⟱
Source:
Type:
Phosphodiesterase 4 (PDE4) has been increasingly implicated in the pathology of Alzheimer's Disease (AD), primarily due to its role in regulating cyclic AMP (cAMP) signaling in the brain.
-Hydrolyzes cAMP → AMP (thus decreasing cAMP levels)
-PDE4 inhibitors (like rolipram): Enhance memory in AD mouse models
Possible inhibitors:
Resveratrol, Baicalin, Luteolin, Quercetin, Apigenin, Icariin


Scientific Papers found: Click to Expand⟱
4986- ATV,  Dipy,    The combination of statins and dipyridamole is effective preclinically in AML, MM, and breast cancer
- Review, Var, NA
HMG-CoA↓, Statins are drugs that have been utilized for years to treat hyperlipidemia through inhibition of the rate-limiting enzyme of the mevalonate (MVA) pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)
AntiAg↑, Dipyridamole (DP), a commonly prescribed anti-platelet agent potentiated the anti-cancer effects of atorvastatin
eff↑, DP-statin combination was synergistic and capable of inducing apoptosis in a variety of acute myelogenous leukemia (AML), MM and breast cancer cell lines.
Apoptosis↑, DP-statin combination also induced apoptosis in primary AML patient samples, but was not toxic to normal PBSCs.
selectivity↑,
*toxicity↓,
TumCG↓, In an in vivo AML tumor model, the DP-statin combination was found to be effective at inhibiting tumor growth.
PDE4↓, DP is known to elicit numerous effects, amongst them, phosphodiesterase (PDE) inhibition
other↑, . As both statins and DP are pre-approved for use in humans, off-patent, and readily available, they have the potential to directly impact patient care.

3785- Bor,    Discovery of boron-containing compounds as Aβ aggregation inhibitors and antioxidants for the treatment of Alzheimer's disease
- Analysis, AD, NA
*Aβ↓, these compounds possessed a significant ability to inhibit self-induced Aβ aggregation (20.5–82.8%, 20 μM) and to act as potential antioxidants
*antiOx↑,
*IronCh↑, Compound 17h also functions as a metal chelator.
*PDE4↓, Some boron-containing compounds have also demonstrated inhibitory activity against the phosphodiesterase 4 enzyme (PDE4) and inflammation-related cytokine release,

6441- SAO,    Sandalwood Album Oil as a Botanical Therapeutic in Dermatology
- Review, PSA, NA
*Inflam↓, anti-inflammatory, anti-microbial, and anti-proliferative agent.
*eff↑, shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum.
*5LO↓, The oil inhibits the oxidative enzyme 5-lipoxygenase and has DPPH radical scavenging activity and,
*DPPH↓,
*hepatoP↑, in vivo, SAO was able to protect mouse livers from damage resulting from oxidative stress and the formation of reactive oxygen species.
*ROS↓,
*PGE2↓, Production of PGE2 was also suppressed, suggesting that SAO might be acting, at least in part, through inhibition of cyclooxygenase
*IL1β↓, The oil also suppressed the expression of the pro-inflammatory cytokine, IL-1b, in keratinocytes and reduced irritant dermatitis in mouse skin stimulated with haptens.
*IL17↓, reduce levels of IL-17 and the activity of PDE4.
*PDE4↓,
*tyrosinase↓, Alpha-santalol was found to be an inhibitor of tyrosinase, a key enzyme in the biosynthetic pathway for the skin pigment melanin.
*AntiFungal↑, SAO has demonstrated potent activity against many fungal dermatophytes and yeasts including Trichophyton, Microsporum and Candida
angioG↓, alpha-santalol, the primary component of SAO, is anti-angiogenic and inhibits the growth of hepatocellular carcinoma and prostate tumors in vitro and in vivo.
TumCG↓,
DNAdam↑, MCF-7) and non-tumorigenic epithelial breast cells (MCF-10A).42 The authors demonstrated that the oil induced deoxyribonucleic acid (DNA) strand breaks in both cell lines.
*Snail↑, SAO enhanced expression of transcription factors (snail, twist) and mesenchymal factor (vimentin), all of which are related to the epithelial-mesenchymal transition (EMT).
*Twist↑,
*Vim↑,
*EMT↓,
*toxicity↓, other species of sandalwood, such as Western Australian (Santalum spicatum) or Hawaiian sandalwood (Santalum paniculatum), contain significant percentages of farnesol, an irritant, that is not found in oil from S. album.


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis(tgid=4) ⓘ

HMG-CoA↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,  

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

TumCG↓, 2,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,   selectivity↑, 1,  

Functional Outcomes(tgid=23) ⓘ

PDE4↓, 1,  
Total Targets: 10

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   DPPH↓, 1,   ROS↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

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

EMT↓, 1,   tyrosinase↓, 1,  

Migration(tgid=13) ⓘ

5LO↓, 1,   Snail↑, 1,   Twist↑, 1,   Vim↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL17↓, 1,   IL1β↓, 1,   Inflam↓, 1,   PGE2↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

hepatoP↑, 1,   PDE4↓, 2,   toxicity↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1,  
Total Targets: 20

Scientific Paper Hit Count for: PDE4, Phosphodiesterase 4
1 Atorvastatin
1 Dipyridamole
1 Boron
1 α-Santalol/Sandalwood oil
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#:%  Target#:1361  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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