Database Query Results : , , Proteasome

Proteasome, Proteasome: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
The proteasome is a crucial component of the cellular machinery responsible for degrading ubiquitinated proteins, which are proteins tagged for destruction. This process is essential for maintaining cellular homeostasis, regulating the cell cycle, and controlling various signaling pathways.
Many cancer cells exhibit increased expression of proteasome subunits. This upregulation can enhance the proteasome's capacity to degrade proteins, including those that regulate cell cycle progression and apoptosis, thereby promoting tumor growth and survival.

Proteasome inhibitors act by blocking the activity of the proteasome, a crucial cellular complex responsible for degrading most intracellular proteins.
-The proteasome is responsible for degrading ubiquitin-tagged proteins, including misfolded, damaged, or regulatory proteins. By inhibiting the proteasome’s function, these proteins accumulate within the cell.
-Accumulated proteins can lead to increased cellular stress, particularly in the endoplasmic reticulum (ER) where misfolded proteins build up. This stress can trigger the unfolded protein response (UPR), which, if unresolved, may lead to apoptosis (programmed cell death).
-It is well known that ROS plays an important role in proteasome inhibition-induced cell death.

Inhibitor Drugs: bortezomib (Velcade) and carfilzomib

Natural Product Inhibitors:
-Gambogic Acid:
-Lactacystin: Origin: Isolated from the bacterium Streptomyces lactacystinaeus.
-Epoxomicin is a highly selective and potent inhibitor of the proteasome. Its structure has informed the design of synthetic drugs such as carfilzomib.
-Syringolin A
-Tyropeptins
-EGCG
-Withania somnifera (commonly known as Ashwagandha).
-Celastrol
Origin: Derived from plants of the Tripterygium genus (commonly known as Thunder God Vine).
Scientific Papers found: Click to Expand⟱
2013- CAP,    Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vivo, NA, NA
TumCP↓, P53↑, P21↑, BAX↑, PSA↓, AR↓, NF-kB↓, Proteasome↓, TumVol↓, eff∅,
5012- DSF,  Cu,    Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems
ROS↑, ALDH↓, TumCP↓, CSCs↓, angioG↓, TumMeta↓, DNAdam↑, Proteasome↓, SOD1↓, GSR↓, ox-GSSG↑, GSH/GSSG↓, MMP↓, Akt↓, cycD1/CCND1↓, NF-kB↓, CSCs↓, MAPK↓, angioG↓, DrugR↓, EMT↓, Vim↓, BioAv↑, eff↑,
4915- DSF,  Cu,    Disulfiram: A novel repurposed drug for cancer therapy
- Review, Var, NA
ROS↑, TumCD↑, NF-kB↓, CSCs↓, ChemoSen↑, RadioS↑, eff↑, selectivity↑, Proteasome?,
1960- GamB,  Vem,    Calcium channel blocker verapamil accelerates gambogic acid-induced cytotoxicity via enhancing proteasome inhibition and ROS generation
- in-vitro, Liver, HepG2 - in-vitro, AML, K562
Proteasome↓, eff↑, Casp↑, ER Stress↑, ROS↑, eff↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned ⓘ

DrugR↓, 1,  

Redox & Oxidative Stress ⓘ

GSH/GSSG↓, 1,   GSR↓, 1,   ox-GSSG↑, 1,   ROS↑, 3,   SOD1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   BAX↑, 1,   Casp↑, 1,   MAPK↓, 1,   Proteasome?, 1,   Proteasome↓, 3,   TumCD↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CSCs↓, 3,   EMT↓, 1,  

Migration ⓘ

TumCP↓, 2,   TumMeta↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 3,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   eff↑, 4,   eff∅, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

TumVol↓, 1,  
Total Targets: 38

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Proteasome, Proteasome
2 Disulfiram
2 Copper and Cu NanoParticlex
1 Capsaicin
1 Gambogic Acid
1 verapamil
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#:262  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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