salinomycin / HO-1 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)


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
4908- Sal,    Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
tumCV↓, ROS↑, lipid-P↑, UPR↑, ER Stress↑, NRF2↓, NADPH↓, HO-1↓, SOD↓, Catalase↓, GPx↓, eff↓, TumCP↓,

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 ⓘ

Catalase↓, 1,   GPx↓, 1,   HO-1↓, 1,   lipid-P↑, 1,   NRF2↓, 1,   ROS↑, 1,   SOD↓, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   UPR↑, 1,  

Migration ⓘ

TumCP↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: HO-1, HMOX1
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#:597  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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