salinomycin / PDKs 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)


PDKs, pyruvate dehydrogenase kinase: Click to Expand ⟱
Source:
Type:
– PDK1 is often upregulated in cancers and is central to the metabolic reprogramming (Warburg effect) that allows tumor cells to favor glycolysis over oxidative phosphorylation.
– Elevated PDK1 expression has been correlated with aggressive tumor behavior and poor prognosis in several cancer types, including non‐small cell lung cancer, ovarian cancer, and gastric cancer.

– Although PDK2 has a similar catalytic role as PDK1, its expression levels and impact may vary.
– Some studies have observed that increased PDK2 expression is associated with more aggressive cancer features and resistance to therapy in certain tumor types.

– PDK3 is often upregulated in response to hypoxic conditions—a common feature of solid tumors—which can further drive metabolic divergence in cancer cells.

– The role of PDK4 appears to be more variable. In some settings, its activity might be lower in tumor cells to favor the use of glycolysis, while in others, it may be upregulated as part of broader metabolic adaptations.

-By upregulating PDKs, cancer cells limit the flux of pyruvate into the mitochondria, thereby promoting glycolysis.
Scientific Papers found: Click to Expand⟱
1884- DCA,  Sal,    Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines
- in-vitro, CRC, DLD1 - in-vitro, CRC, HCT116
eff↑, pH↓, PDKs↓, Warburg↓,
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↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

OXPHOS↑, 1,   ROS↑, 2,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

Apoptosis↑, 1,   Casp3↑, 1,   Cyt‑c↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

LC3s↓, 1,   p62↑, 1,   TumAuto↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   mTOR↓, 1,   TumCG↓, 2,  

Cellular Microenvironment ⓘ

pH↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 4,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

Ferritin↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   toxicity↝, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: PDKs, pyruvate dehydrogenase kinase
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#:1201  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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