salinomycin / Apoptosis 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)


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.
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↓,
5002- Sal,  SFN,    Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo
- in-vivo, CRC, Caco-2 - vitro+vivo, CRC, CX-1
Apoptosis↑, PI3K↓, Akt↓, P53↑, BAX↑, Bax:Bcl2↑, p‑PARP↑, TumCMig↓,
5123- Sal,    Salinomycin suppresses LRP6 expression and inhibits both Wnt/β-catenin and mTORC1 signaling in breast and prostate cancer cells
- in-vitro, BC, MCF-7 - in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, BC, MDA-MB-231 - in-vitro, Nor, HEK293
Wnt↓, β-catenin/ZEB1↓, mTORC1↓, GSK‐3β↑, cycD1/CCND1↓, survivin↓, LRP6↓, TumCG↓, Apoptosis↑,
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↑,
4907- Sal,    A comprehensive review of salinomycin derivatives as potent anticancer and anti-CSCs agents
- Review, Var, NA
Apoptosis↑, MDR1↓, CSCs↓,
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↑,
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↑,
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↑,
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⇅,
4994- Sal,  Rad,    Salinomycin overcomes radioresistance in nasopharyngeal carcinoma cells by inhibiting Nrf2 level and promoting ROS generation
AntiCan↑, RadioS↓, Apoptosis↑, NRF2↓, ROS↑, DNAdam↑,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   GSH↓, 1,   Iron↑, 1,   MDA↑, 1,   NRF2↓, 1,   OXPHOS↓, 2,   OXPHOS↑, 1,   ROS↑, 9,   SOD↓, 1,   SOD1↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 3,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 12,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 2,   Casp3↑, 4,   Casp9↑, 1,   Cyt‑c↑, 1,   MAPK↑, 1,   Myc↓, 1,   necrosis↑, 1,   p27↑, 1,   survivin↓, 2,   TumCD↑, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

LC3s↓, 1,   p62↑, 1,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   P53↑, 2,   p‑P53↑, 1,   p‑PARP↑, 1,   cl‑PARP↝, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 3,   P21↑, 2,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   CSCs↓, 6,   CSCs↑, 1,   Diff↑, 1,   EMT↓, 1,   Gli1↓, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   LRP6↓, 1,   mTOR↓, 2,   mTORC1↓, 1,   PI3K↓, 1,   PTCH1↓, 1,   Smo↓, 1,   TumCG↓, 6,   Wnt↓, 5,  

Migration ⓘ

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

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   ChemoSen↑, 5,   Dose↝, 1,   eff↓, 1,   eff↑, 5,   MDR1↓, 1,   RadioS↓, 1,   RadioS↑, 3,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,   Ferritin↓, 2,   LDH↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   OS↑, 1,   toxicity⇅, 1,   toxicity↝, 1,  
Total Targets: 96

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Apoptosis, Apoptosis
12 salinomycin
1 Dichloroacetate
1 Sulforaphane (mainly Broccoli)
1 Silver-NanoParticles
1 Oxaliplatin
1 Radiotherapy/Radiation
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#:14  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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