SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells.

Autor: Krabbendam IE; Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: i.e.krabbendam@rug.nl., Honrath B; Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands., Bothof L; Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands., Silva-Pavez E; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Chile and Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Huerta H; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Chile and Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Peñaranda Fajardo NM; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Dekker F; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Groningen, the Netherlands., Schmidt M; Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands., Culmsee C; Institut für Pharmakologie und Klinische Pharmazie, Biochemisch-Pharmakologisches Centrum Marburg, Philipps-Universität Marburg, Karl-von-Frisch-Straße 2, Marburg 35032, Germany; Center for Mind, Brain and Behavior, Universities of Marburg and Gießen, Hans-Meerwein-Straße 6, 35032 Marburg, Germany., César Cárdenas J; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Chile and Geroscience Center for Brain Health and Metabolism, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, United States; Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, United States., Kruyt F; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Dolga AM; Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: a.m.dolga@rug.nl.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2020 Jan; Vol. 171, pp. 113714. Date of Electronic Publication: 2019 Nov 15.
DOI: 10.1016/j.bcp.2019.113714
Abstrakt: Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/K Ca ) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyPPA to activate SK channels in neuro- and glioblastoma cells. Combined treatment with auranofin and CyPPA induced massive mitochondrial damage and potentiated auranofin-induced toxicity in neuroblastoma cells in vitro. In particular, mitochondrial integrity, respiration and associated energy generation were impaired. These findings were recapitulated in patient-derived glioblastoma neurospheres yet not observed in non-cancerous HT22 cells. Taken together, integrating auranofin and SK channel openers to affect mitochondrial health was identified as a promising strategy to increase the effectiveness of anti-cancer agents and potentially overcome resistance.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: