Disulfiram / CREB Cancer Research Results

DSF, Disulfiram: Click to Expand ⟱
Features:
Disulfiram is a synthetic small-molecule drug best known for its use in the treatment of chronic alcohol use disorder. It is a thiuram disulfide compound with the chemical formula C₁₀H₂₀N₂S₄ and acts primarily as an aldehyde dehydrogenase (ALDH) inhibitor. 
Main Actions:
-Potent copper-dependent pro-oxidant
-Targets ALDH⁺ cancer stem cells
-Strong clinical repurposing interest

Key pathways
-Cu-mediated redox cycling
-Proteasome inhibition
-Mitochondrial ROS

Chemo relevance
-Often synergistic
-Highly mechanism-dependent
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Metal chelation / Disulfiram–Cu complex formation ↑ DSF–Cu complex formation ↔ limited formation Driver Copper-dependent cytotoxic chemistry Elevated copper in cancer cells enables formation of cytotoxic DSF–Cu complexes; this is the initiating event for most anticancer effects
2 Proteasome / p97–NPL4 axis ↓ proteasome function; ↑ proteotoxic stress ↔ minimal disruption Driver Protein homeostasis collapse DSF–Cu disrupts protein degradation pathways, leading to accumulation of misfolded proteins and stress signaling
3 Reactive oxygen species (ROS) ↑ ROS (metal-dependent) ↔ buffered Secondary Oxidative stress amplification ROS rise follows DSF–Cu redox cycling and proteotoxic stress; not the primary trigger
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of cell death Mitochondrial dysfunction and apoptosis occur downstream of proteostasis and redox stress
5 ALDH activity (ALDH1A1 / stemness) ↓ ALDH activity ↓ ALDH (clinically tolerated) Secondary Cancer stem-like cell targeting ALDH inhibition preferentially impacts cancer stem-like populations; normal cells tolerate inhibition at therapeutic exposure
6 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival transcription NF-κB inhibition reflects upstream proteotoxic and redox stress rather than direct targeting
7 Cell cycle progression ↓ proliferation / ↑ arrest ↔ largely spared Phenotypic Cytostatic growth control Growth inhibition reflects impaired protein turnover and metabolic stress
8 Apoptosis / non-apoptotic death ↑ apoptosis or proteotoxic death ↔ protected Phenotypic Threshold-dependent cell death Cell death modality depends on copper availability and stress magnitude


CREB, cAMP Response Element Binding Protein: Click to Expand ⟱
Source:
Type: transcription factor
CREB is a transcription factor that binds to specific DNA sequences, known as cAMP response elements (CRE), in the promoter regions of target genes.
CREB is activated by phosphorylation, which allows it to bind to CRE and recruit other transcriptional coactivators.
CREB regulates the expression of genes involved in various cellular processes, including:
    Cell growth and differentiation
    Apoptosis
    Metabolism
    Neurotransmission

CREB is also involved in the regulation of genes involved in cancer, including:
    Cell cycle progression
    Angiogenesis
    Invasion and metastasis

CREB is often overexpressed in cancer tissues.
High levels of CREB expression are associated with poor prognosis, increased tumor aggressiveness, and resistance to therapy. CREB can promote the expression of genes involved in cell survival and proliferation.
Scientific Papers found: Click to Expand⟱
5013- DSF,  Cu,  Z,    Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease
- vitro+vivo, Melanoma, NA - Case Report, Melanoma, NA
P-gp↓, NF-kB↓, ChemoSen↑, angioG↓, TumCG↓, TumMeta↓, Remission↑, toxicity↓, ATF2↓, CREB↓, cycA1/CCNA1↓, TumCG↓, angioG↓, Dose↝, toxicity↝,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

CREB↓, 1,  

Cell Death ⓘ

ATF2↓, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 2,  

Migration ⓘ

TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,  

Functional Outcomes ⓘ

Remission↑, 1,   toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CREB, cAMP Response Element Binding Protein
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#:387  Target#:798  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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