salinomycin / RadioS 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)


RadioS, RadioSensitizer: Click to Expand ⟱
Source:
Type:
A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes.
Pathways that help Radiosensitivity: downregulating HIF-1α, increase SIRT1, Txr

List of Natural Products with radiosensitizing properties:
-Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways.
-Resveratrol:
-EGCG:
-Quercetin:
-Genistein:
-Parthenolide:

How radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including:
-gold nanoparticles (GNPs),
-gold triethylphosphine cyanide ([Au(SCN) (PEt3)]),
-auranofin, ceria nanoparticles (CONPs),
-curcumin and its derivatives,
-piperlongamide,
-indolequinone derivatives,
-micheliolide,
-motexafin gadolinium, and
-ethane selenide selenidazole derivatives (SeDs)


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↑,
4898- Sal,    Salinomycin as a potent anticancer stem cell agent: State of the art and future directions
- Review, Var, NA
CSCs↓, AntiCan↑, ChemoSen↑, RadioS↑, Wnt↓, MAPK↓, TumAuto↑, ATP↓, ROS↑, DNAdam↑, ER Stress↑, CSCsMark↓, Iron↑, *toxicity↝,
4902- Sal,  OXA,    Salinomycin and oxaliplatin synergistically enhances cytotoxic effect on human colorectal cancer cells in vitro and in vivo
- vitro+vivo, CRC, NA
RadioS↑, ChemoSen↑, TumCP↓, Apoptosis↑, ROS↑, MMP↓, MAPK↑, eff↓, TumCG↓, TumCCA↑,
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 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

Iron↑, 1,   OXPHOS↑, 1,   ROS↑, 5,  

Metal & Cofactor Biology

Ferritin↓, 1,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis

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

Cell Death

Apoptosis↑, 3,   Casp3↑, 1,   Cyt‑c↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,  

Protein Folding & ER Stress

ER Stress↑, 3,  

Autophagy & Lysosomes

LC3s↓, 1,   p62↑, 1,   TumAuto↑, 3,  

DNA Damage & Repair

DNAdam↑, 2,  

Cell Cycle & Senescence

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

CSCs↓, 4,   CSCsMark↓, 1,   EMT↓, 1,   mTOR↓, 1,   Shh↓, 1,   TumCG↓, 3,   Wnt↓, 3,  

Migration

TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Barriers & Transport

P-gp↓, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 5,   eff↓, 2,   eff↑, 3,   RadioS↑, 5,   selectivity↑, 3,  

Clinical Biomarkers

Ferritin↓, 1,  

Functional Outcomes

AntiCan↑, 1,   OS↑, 1,   toxicity⇅, 1,   toxicity↝, 1,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Functional Outcomes

toxicity↝, 1,  
Total Targets: 1

Scientific Paper Hit Count for: RadioS, RadioSensitizer
5 salinomycin
1 Dichloroacetate
1 Oxaliplatin
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#:1107  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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