Disulfiram / TumCI 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


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
4916- DSF,  Cu,    The immunomodulatory function and antitumor effect of disulfiram: paving the way for novel cancer therapeutics
- Review, Var, NA
TumCP↓, TumCMig↓, TumCI↓, eff↑, Imm↑, ROS↑, NF-kB↓, chemoP↑, JNK↑, FOXO↑, Myc↑, TumCCA↑, Apoptosis↑, RadioS↑, PD-L1↑, eff↑, CSCs↓, Dose↝, Half-Life↑,
5008- DSF,  Cu,    Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis
- in-vitro, HCC, NA
selectivity↑, TumCD↑, TumCMig↓, TumCI↓, angioG↓, mtDam↑, Iron↑, lipid-P↑, Ferroptosis↑, NF-kB↑, p‑p62↑, Keap1↓, eff↑, eff↓, ChemoSen↑,

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 ⓘ

Ferroptosis↑, 1,   Iron↑, 1,   Keap1↓, 1,   lipid-P↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

mtDam↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   Myc↑, 1,   TumCD↑, 1,  

Autophagy & Lysosomes ⓘ

p‑p62↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   FOXO↑, 1,  

Migration ⓘ

TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

Imm↑, 1,   NF-kB↓, 1,   NF-kB↑, 1,   PD-L1↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 3,   Half-Life↑, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

Myc↑, 1,   PD-L1↑, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,  
Total Targets: 33

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
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#:324  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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