salinomycin / selectivity 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)


selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
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↓,
5003- Sal,    Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review
- Review, Var, NA
CSCs↓, TumAuto↑, selectivity↑, DNAdam↑, TumCCA↑, P-gp↓, Wnt↓, β-catenin/ZEB1↓, RadioS↑, ChemoSen↑, Shh↓, eff↓, ROS↑, AMPK↑, JNK↑, ER Stress↑,
5121- Sal,    Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells
- in-vitro, BC, NA
CSCs↓, Wnt↓, selectivity↑,
5122- Sal,    Identification of selective inhibitors of cancer stem cells by high-throughput screening
- in-vivo, BC, SUM159 - NA, NA, 4T1
CSCs↓, TumCG↓, Diff↑, selectivity↑, CD44↓, CD24↓, TumVol↓,
4899- Sal,    Anticancer activity of salinomycin quaternary phosphonium salts
- in-vitro, Var, NA
eff↑, selectivity↑, CSCs↓, TumCCA↑, MMP↓, ROS↑, mitResp↑,
4903- Sal,    Salinomycin: A new paradigm in cancer therapy
- Review, Var, NA
TumCG↓, ATP↓, CSCs↓, ROS↑, Casp↑, MMP↓, selectivity↑, OXPHOS↓, STAT3↓, P53↑, γH2AX↑, cycD1/CCND1↓, TumCCA↑, DNAdam↑, ChemoSen↑,
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↝,
4996- Sal,    The Molecular Basis for Inhibition of Stemlike Cancer Cells by Salinomycin
CSCs↓, selectivity↑, Wnt↓, ERStress↑, Ca+2↓, UPR↑, CHOP↑, β-catenin/ZEB1↓, CD44↓, CD24↓, PKCδ↑,
4910- Sal,    A medicinal chemistry perspective on salinomycin as a potent anticancer and anti-CSCs agent
Apoptosis↑, CSCs↓, ChemoSen↑, RadioS↑, selectivity↑, Wnt↓, toxicity⇅,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

OXPHOS↓, 2,   OXPHOS↑, 1,   ROS↑, 6,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   mitResp↑, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PDKs↓, 1,  

Cell Death ⓘ

Apoptosis↑, 3,   Casp↑, 1,   Casp3↑, 2,   Cyt‑c↑, 1,   JNK↑, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 2,   ERStress↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

LC3s↓, 1,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 2,   CD44↓, 2,   CSCs↓, 9,   Diff↑, 2,   EMT↓, 1,   mTOR↓, 1,   Shh↓, 1,   STAT3↓, 1,   TumCG↓, 4,   Wnt↓, 5,  

Migration ⓘ

Ca+2↓, 1,   Fibronectin↓, 1,   PKCδ↑, 1,   β-catenin/ZEB1↓, 2,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 4,   Dose↝, 1,   eff↓, 1,   eff↑, 4,   RadioS↑, 3,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

Ferritin↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   toxicity⇅, 1,   toxicity↝, 1,   TumVol↓, 1,  
Total Targets: 55

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: selectivity, selectivity
9 salinomycin
1 Dichloroacetate
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#:1110  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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