ArticleCancer cell international2019
The ionophore antibiotic gramicidin A inhibits pancreatic cancer stem cells associated with CD47 down-regulation.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Colloidal Dispersions of Gramicidin D in Water: Preparation, Characterization, and Differential Cytotoxicity.ACS omega · 2025Article
- Therapeutic strategies targeting CD47-SIRPα signaling pathway in gastrointestinal cancers treatment.Journal of pharmaceutical analysis · 2025Review
- CD47: an immunoregulatory nexus in liver and gastrointestinal disorders.eGastroenterology · 2025Review
- Cancer stem cells: advances in the glucose, lipid and amino acid metabolism.Molecular and cellular biochemistry · 2024Review
- Gramicidin, a Bactericidal Antibiotic, Is an Antiproliferative Agent for Ovarian Cancer Cells.Medicina (Kaunas, Lithuania) · 2023Article
- Transient Coatings from Nanoparticles Achieving Broad-Spectrum and High Antimicrobial Performance.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Target c-Myc to treat pancreatic cancer.Cancer biology & therapy · 2022Article
- Gramicidin A accumulates in mitochondria, reduces ATP levels, induces mitophagy, and inhibits cancer cell growth.Chemical science · 2022Article
- Antibiotic use influences outcomes in advanced pancreatic adenocarcinoma patients.Cancer medicine · 2021Article
- A Note of Caution: Gramicidin Affects Signaling Pathways Independently of Its Effects on Plasma Membrane Conductance.BioMed research international · 2021Article
- Antimicrobial Peptides as New Combination Agents in Cancer Therapeutics: A Promising Protocol against HT-29 Tumoral Spheroids.International journal of molecular sciences · 2020Article
- Checkpoint CD47 Function On Tumor Metastasis And Immune Therapy.OncoTargets and therapy · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer stem cells (CSCs), a special population of cells, renew themselves infinitely and resist to various treatment. Gramicidin A (GrA), an ionophore antibiotic derived from microorganism, can form channels across the cell membrane and disrupt cellular ionic homeostasis, leading to cell dysfunction and death. As reported, the ionophore antibiotic salinomycin (Sal) has been proved to kill CSCs effectively. Whether GrA owns the potential as a therapeutic drug for CSCs still remains unknown. This study investigated the effect of GrA on pancreatic CSCs and the mechanism.
methodsTumorsphere formation assay was performed to assess pancreatic CSCs self-renewal potential. In vitro hemolysis assay was determined to test the borderline concentration of GrA. CCK-8 assay was used to detect pancreatic cancer cell proliferation capability. Flow cytometry was performed to detect cell apoptosis and mitochondrial membrane potential. Scanning and transmission electron microscopy was used to observe ultrastructural morphological changes on cell membrane surface and mitochondria, respectively. Western blot analysis was used to determine relative protein expression levels. Immunofluorescence staining was performed to observe CD47 re-distribution.
resultsGrA at 0.05 μM caused tumorspheres disintegration and decrease in number of pancreatic cancer BxPC-3 and MIA PaCa-2 cells. GrA and Sal both inhibited cancer cell proliferation. The IC50 values of GrA and Sal for BxPC-3 cells were 0.025 μM and 0.363 μM; while for MIA PaCa-2 cells were 0.032 μM and 0.163 μM, respectively. Compared on equal concentrations, the efficacy of GrA was stronger than that of Sal. GrA at 0.1 μM or lower did not cause hemolysis. GrA induced ultrastructural changes, such as the decrease of microvilli-like protrusions on cell surface membrane and the swelling of mitochondria. GrA down-regulated the expression levels of CD133, CD44, and CD47; in addition, CD47 re-distribution was observed on cell surface. Moreover, GrA showed synergism with gemcitabine in suppressing cancer cell proliferation.
conclusionsThe study found that GrA was highly active against pancreatic CSCs. It indicates that GrA exerts inhibitory effects against pancreatic CSCs associated with CD47 down-regulation, implying that GrA might play a positive role in modulating the interaction between macrophages and tumor cells.
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