salinomycin / Casp3 Cancer Research Results

Sal, salinomycin: Click to Expand ⟱
Features:
Salinomycin is a polyether ionophore antibiotic that is produced by the bacterium Streptomyces albus. It was first isolated in 1979 and has been found to have a range of biological activities, including antibacterial, antifungal, and anticancer properties.
It has been shown to induce apoptosis (programmed cell death) in a range of cancer cell lines, including breast, lung, and colon cancer cells. Salinomycin has also been found to inhibit the growth of cancer stem cells.
Salinomycin, a widely used antibiotic in poultry farming
Actions:
-Strong activity against cancer stem cells
-Disrupts mitochondrial ion gradients → ROS
-Non-thiol, non-NRF2 dominant

Key pathways
-Mitochondrial K⁺ dysregulation
-ROS-mediated apoptosis
-Wnt/β-catenin inhibition

Chemo relevance
-Generally compatible or synergistic
-Not a redox buffer

Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 K+ ionophore activity / ionic homeostasis ↑ K+ transport (ionophore) / ↓ intracellular K+ homeostasis Electrochemical disruption Salinomycin is directly described as a potassium ionophore in mechanistic studies of its anticancer effects (ref)
2 Cancer stem cell (CSC) fraction / stemness programs ↓ CSC proportion / tumor-initiating capacity Selective CSC depletion Landmark study showing salinomycin strongly reduces CSC proportion (e.g., >100-fold vs paclitaxel in their assay context) and inhibits tumor growth in vivo (ref)
3 Wnt/β-catenin signaling ↓ Loss of self-renewal signaling Primary mechanistic paper identifying salinomycin as an inhibitor of the Wnt signaling cascade (ref)
4 Wnt co-receptor LRP6 (Wnt pathway control point) ↓ LRP6 / ↓ Wnt signaling Wnt pathway suppression Shows salinomycin suppresses LRP6 expression at concentrations relevant to growth inhibition, linking activity to Wnt/β-catenin suppression (ref)
5 Autophagic flux + lysosomal proteolysis ↓ autophagic flux (blocked) / ↓ lysosomal proteolytic activity Abortive autophagy / stress accumulation Demonstrates salinomycin blocks autophagic flux and lysosomal proteolytic activity in breast cancer CSC and non-CSC populations (ref)
6 ER stress / UPR (ATF4 → CHOP/DDIT3) ↑ ER stress / ↑ CHOP axis Proteotoxic stress signaling Shows salinomycin stimulates ER stress and mediates autophagy through the ATF4–CHOP–TRIB3 axis (ref)
7 AKT–mTOR survival signaling (via TRIB3) ↓ AKT / ↓ mTOR signaling Reduced survival + altered autophagy control Same mechanistic work links ER stress activation to TRIB3-mediated inhibition of AKT1–mTOR signaling after salinomycin exposure (ref)
8 ROS generation and ROS-linked lysosomal dysfunction ↑ ROS Oxidative stress amplification Demonstrates salinomycin-induced ROS and connects ROS to lysosomal membrane permeability and impaired autophagy flux (ref)
9 Mitochondrial apoptosis (caspase cascade) ↑ Caspase-9/3 activation Programmed cell death Shows salinomycin triggers caspase-dependent apoptosis involving caspases (including 9 and 3) in a salinomycin toxicity/mechanism study (demonstrates directionality for caspase activation) (ref)
10 EMT phenotype ↑ E-cadherin / ↓ vimentin (EMT suppressed) Reduced migration/invasion Reports salinomycin increases epithelial markers and decreases mesenchymal markers in a dose-dependent manner, with reduced migration/invasion (ref)
11 ABC transporter–mediated multidrug resistance ↓ functional MDR phenotype Overcomes drug resistance Directly reports salinomycin overcomes ABC transporter–mediated multidrug/apoptosis resistance in leukemia stem cell–like cells (ref)
12 Ferroptosis susceptibility (GPX4 axis) in CSC context ↑ ferroptosis (context-dependent) Non-apoptotic oxidative death modality Reports salinomycin induces ferroptosis in a CSC context via a pathway converging on GPX4/GPX activity regulation (directionality: ferroptosis induction by salinomycin in that model) (ref)


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
4901- DCA,  Sal,    Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer
- Review, NSCLC, NA
Glycolysis↓, OXPHOS↑, PDKs↓, ROS↑, Apoptosis↑, GlucoseCon↓, lactateProd↓, RadioS↑, TumAuto↑, mTOR↓, LC3s↓, p62↑, TumCG↓, OS↑, toxicity↝, ChemoSen↑, eff↑, eff↑, Ferritin↓, CSCs↓, EMT↓, ROS↑, Cyt‑c↑, Casp3↑, ER Stress↑, selectivity↑, eff↑, TumCG↓,
5126- Sal,    Salinomycin induces calpain and cytochrome c-mediated neuronal cell death
CSCs↓, Ca+2↑, cal2↑, Casp12↑, Casp9↑, Casp3↑, Cyt‑c↑, MMP↓,
323- Sal,  AgNPs,    Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy
- in-vitro, BC, MDA-MB-231 - in-vitro, Ovarian, A2780S
TumCD↑, LDH↓, MDA↑, SOD↓, ROS↑, GSH↓, Catalase↓, MMP↓, P53↑, P21↑, BAX↑, Bcl-2↓, Casp3↑, Casp9↑, Apoptosis↑, TumAuto↑,
4905- Sal,    Salinomycin as a drug for targeting human cancer stem cells
- Review, Var, NA
CSCs↓, selectivity↑, Apoptosis↑, Casp3↑, ROS↑, Wnt↓, cycD1/CCND1↓, Fibronectin↓, OXPHOS↓, Diff↑, Dose↝,
4906- Sal,    A Concise Review of Prodigious Salinomycin and Its Derivatives Effective in Treatment of Breast Cancer: (2012–2022)
- Review, BC, NA
CSCs↓, Casp3↑, cl‑PARP↝, Apoptosis↑, ROS↑, ABC↓, OXPHOS↓, Glycolysis↓, eff↑, TumAuto↑, DNAdam↑, Wnt↓, Ferritin↓, Iron↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   GSH↓, 1,   Iron↑, 1,   MDA↑, 1,   OXPHOS↓, 2,   OXPHOS↑, 1,   ROS↑, 5,   SOD↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   Glycolysis↓, 2,   lactateProd↓, 1,   LDH↓, 1,   PDKs↓, 1,  

Cell Death ⓘ

Apoptosis↑, 4,   BAX↑, 1,   Bcl-2↓, 1,   Casp12↑, 1,   Casp3↑, 5,   Casp9↑, 2,   Cyt‑c↑, 2,   TumCD↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

LC3s↓, 1,   p62↑, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↝, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 4,   Diff↑, 1,   EMT↓, 1,   mTOR↓, 1,   TumCG↓, 2,   Wnt↓, 2,  

Migration ⓘ

Ca+2↑, 1,   cal2↑, 1,   Fibronectin↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↑, 4,   RadioS↑, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

Ferritin↓, 2,   LDH↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   toxicity↝, 1,  
Total Targets: 51

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
5 salinomycin
1 Dichloroacetate
1 Silver-NanoParticles
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#:203  Target#:42  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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