salinomycin / ABC 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)


ABC, ABC transporter: Click to Expand ⟱
Source:
Type:
ABC (ATP-binding cassette) transporters are a family of proteins that play a crucial role in the transport of various molecules across cell membranes.
ABC transporters have been implicated in the development of multidrug resistance, which is a major obstacle in cancer treatment.
Overexpression of certain ABC transporters, such as P-glycoprotein (P-gp), has been observed in various types of cancer, including breast, lung, and colon cancer.
Examples of ABC transporters implicated in cancer include:
- P-glycoprotein (P-gp, ABCB1)
- Multidrug resistance-associated protein 1 (MRP1, ABCC1)
- Breast cancer resistance protein (BCRP, ABCG2)
Prognostic Implications
-Drug Resistance: High expression of ABC transporters is often linked to resistance against chemotherapy, leading to treatment failure and poor patient outcomes.
-Survival Rates: Patients with tumors expressing high levels of certain ABC transporters may have lower overall survival rates.
Target for Therapy: Inhibitors of ABC transporters are being explored as potential adjuncts to improve the efficacy of chemotherapy.
Scientific Papers found: Click to Expand⟱
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↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Iron↑, 1,   OXPHOS↓, 1,   ROS↑, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Casp3↑, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   cl‑PARP↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   Wnt↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

Ferritin↓, 1,  
Total Targets: 15

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: ABC, ABC transporter
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#:621  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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