Disulfiram / MAPK 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


MAPK, mitogen-activated protein kinase: Click to Expand ⟱
Source: CGL-CS
Type:
Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.
Scientific Papers found: Click to Expand⟱
4914- DSF,  immuno,    Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies
- Review, Var, NA
AntiTum↑, eff↑, ALDH↓, Dose↝, RadioS↑, angioG↓, TumMeta↓, BioAv↝, ROS↑, DNAdam↑, P-gp↓, CSCs↓, EMT↓, Imm↑, SOD↓, MAPK↓, NF-kB↓, ChemoSen↑, eff↑, toxicity↝, BioAv↑, *Inflam↓, Sepsis↓,
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↑,

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:


Redox & Oxidative Stress ⓘ

GSH/GSSG↓, 1,   GSR↓, 1,   ox-GSSG↑, 1,   ROS↑, 2,   SOD↓, 1,   SOD1↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   MAPK↓, 2,   Proteasome↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   CSCs↓, 3,   EMT↓, 2,  

Migration ⓘ

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

Angiogenesis & Vasculature ⓘ

angioG↓, 3,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

Imm↑, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↝, 1,   DrugR↓, 1,   eff↑, 3,   RadioS↑, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   toxicity↝, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase
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#:181  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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