salinomycin / CSCs 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)


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.

Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review
Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy
Can we utilise the circadian clock to target cancer stem cells?
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↓,
4997- Sal,    Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy
- in-vitro, BC, NA
CD24↓, TumCP↓, CSCs↓,
5128- Sal,    Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells
- in-vitro, AML, NA
CSCs↓,
4998- Sal,    Salinomycin may inhibit the cancer stem-like populations with increased chemoradioresistance that nasopharyngeal cancer tumorspheres contain
- in-vitro, NPC, NA
CSCs↓,
4999- Sal,    Salinomycin triggers endoplasmic reticulum stress through ATP2A3 upregulation in PC-3 cells
- in-vitro, Pca, PC3
Bacteria↓, CSCs↓, ER Stress↑,
5001- Sal,    Salinomycin exerts anti‐colorectal cancer activity by targeting the β‐catenin/T‐cell factor complex
- in-vitro, CRC, NA
CSCs↓, β-catenin/ZEB1↓, Wnt↓,
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↑,
5004- Sal,    Targeting Telomerase Enhances Cytotoxicity of Salinomycin in Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
eff↑, AntiCan↑, CSCs↑, Wnt↓, β-catenin/ZEB1↓, Diff↑, ROS↑, toxicity↝, selectivity↝, eff↑,
5005- Sal,    Salinomycin Derivatives Kill Breast Cancer Stem Cells by Lysosomal Iron Targeting
- Review, Var, NA
CSCs↑,
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↓,
5124- Sal,    Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance
- in-vitro, BC, NA
CSCs↓, LC3II↑, other↓, lysosome↓, CTSZ↓, CTSB↓, CTSL↓, CTSS↓, autoF↓, TumAuto↓,
5125- Sal,    Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma
- in-vitro, GBM, NA
ER Stress↑, UPR↑, autoF↓, lysosome↝, ROS↑, lipid-P↑, CSCs↓, necrosis↑, ATP↓, MMP↓, MOMP↑, DNAdam↑, AIF↑, lysoMP↑, MitoP↑, Ca+2↑,
5126- Sal,    Salinomycin induces calpain and cytochrome c-mediated neuronal cell death
CSCs↓, Ca+2↑, cal2↑, Casp12↑, Casp9↑, Casp3↑, Cyt‑c↑, MMP↓,
4907- Sal,    A comprehensive review of salinomycin derivatives as potent anticancer and anti-CSCs agents
- Review, Var, NA
Apoptosis↑, MDR1↓, CSCs↓,
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↝,
4899- Sal,    Anticancer activity of salinomycin quaternary phosphonium salts
- in-vitro, Var, NA
eff↑, selectivity↑, CSCs↓, TumCCA↑, MMP↓, ROS↑, mitResp↑,
4900- Sal,    Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications
- Review, BC, NA
CSCs↓, Apoptosis↑, TumAuto↑, necrosis↑, TumCP↓, TumCI↓, TumCMig↓, TumCG↓, TumMeta↓, eff↑, Bcl-2↓, cMyc↓, Snail↓, ALDH↓, Myc↓, AR↓, ROS↑, NF-kB↓, PTCH1↓, Smo↓, Gli1↓, GLI2↓, Wnt↓, mTOR↓, GSK‐3β↓, cycD1/CCND1↓, survivin↓, P21↑, p27↑, CHOP↑, Ca+2↑, DNAdam↑, Hif1a↓, VEGF↓, angioG↓, MMP↓, ATP↓, p‑P53↑, γH2AX↑, ChemoSen↑,
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↑,
4904- Sal,  CUR,    Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition
CSCs↓, TumCCA↑, EMT↓, other↝, TumAuto↑, Iron↑, Ferroptosis↑, BioAv↓, ROS↑, lipid-P↑, GPx4↓, eff↑,
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↑,
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↑,
4909- Sal,    Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model
- vitro+vivo, CRC, NA
AntiTum↑, Apoptosis↑, mtDam↑, ROS↑, SOD1↓, ChemoSen↑, CSCs↑, ALDH↓, TumCG↓, TumCP↓, TumCD↑, ATP↓,
4910- Sal,    A medicinal chemistry perspective on salinomycin as a potent anticancer and anti-CSCs agent
Apoptosis↑, CSCs↓, ChemoSen↑, RadioS↑, selectivity↑, Wnt↓, toxicity⇅,
4911- Sal,    MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells
- in-vitro, Var, DU145
MUC1-C↓, Ferroptosis↑, CSCs↓, NF-kB↓, GSR↓, GSH↑, Iron↑,
4912- Sal,    Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells
- in-vitro, Lung, A549 - in-vitro, Lung, H460 - in-vitro, Lung, Calu-1 - in-vitro, Lung, H157
CSCs↓, TumAuto↑, ER Stress↑, TumCD↑, ATF4↑, CHOP↑, AKT1↓, mTOR↓,
4995- Sal,    Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway
- vitro+vivo, BC, MDA-MB-231
ALDH↓, Nanog↓, OCT4↓, SOX2↓, CSCs↓, tumCV↓, cycD1/CCND1↓, P21↑, TumCG↓, CD44↓, Apoptosis∅,

Showing Research Papers: 1 to 28 of 28

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 28

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 2,   GPx4↓, 1,   GSH↑, 1,   GSR↓, 1,   Iron↑, 4,   lipid-P↑, 2,   OXPHOS↓, 3,   OXPHOS↑, 1,   ROS↑, 13,   SOD1↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 2,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 5,   mitResp↑, 1,   MMP↓, 5,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   AMPK↑, 1,   cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   lactateProd↓, 1,   PDKs↓, 1,  

Cell Death ⓘ

Apoptosis↑, 7,   Apoptosis∅, 1,   Bcl-2↓, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↑, 4,   Casp9↑, 1,   Cyt‑c↑, 2,   Ferroptosis↑, 2,   JNK↑, 1,   lysoMP↑, 1,   MAPK↓, 1,   MOMP↑, 1,   Myc↓, 1,   necrosis↑, 2,   p27↑, 1,   survivin↓, 1,   TumCD↑, 2,  

Transcription & Epigenetics ⓘ

other↓, 1,   other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   ER Stress↑, 6,   ERStress↑, 1,   UPR↑, 2,  

Autophagy & Lysosomes ⓘ

autoF↓, 2,   LC3II↑, 1,   LC3s↓, 1,   lysosome↓, 1,   lysosome↝, 1,   MitoP↑, 1,   p62↑, 1,   TumAuto↓, 1,   TumAuto↑, 7,  

DNA Damage & Repair ⓘ

DNAdam↑, 6,   P53↑, 1,   p‑P53↑, 1,   cl‑PARP↝, 1,   γH2AX↑, 2,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 4,   P21↑, 2,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 3,   CD24↓, 3,   CD44↓, 3,   CSCs↓, 25,   CSCs↑, 3,   CSCsMark↓, 1,   CTSB↓, 1,   CTSL↓, 1,   CTSS↓, 1,   Diff↑, 3,   EMT↓, 2,   Gli1↓, 1,   GSK‐3β↓, 1,   mTOR↓, 3,   Nanog↓, 1,   OCT4↓, 1,   PTCH1↓, 1,   Shh↓, 1,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 1,   TumCG↓, 7,   Wnt↓, 10,  

Migration ⓘ

Ca+2↓, 1,   Ca+2↑, 3,   cal2↑, 1,   Fibronectin↓, 1,   GLI2↓, 1,   MUC1-C↓, 1,   PKCδ↑, 1,   Snail↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   TumMeta↓, 1,   β-catenin/ZEB1↓, 4,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

CTSZ↓, 1,   NF-kB↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   BioAv↓, 1,   ChemoSen↑, 7,   Dose↝, 1,   eff↓, 1,   eff↑, 9,   MDR1↓, 1,   RadioS↑, 4,   selectivity↑, 9,   selectivity↝, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   Ferritin↓, 2,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,   OS↑, 1,   toxicity⇅, 1,   toxicity↝, 2,   TumVol↓, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 129

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity↝, 1,  
Total Targets: 1

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
28 salinomycin
1 Dichloroacetate
1 Curcumin
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#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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