The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells
Despite great efforts to develop new therapeutic strategies to combat melanoma, the prognosis remains rather poor. Artesunate (ART) is an antimalarial drug displaying anti-cancer effects in vitro and in vivo. In this in vitro study, we investigated the selectivity of ART on melanoma cells. Furthermo...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2393 |
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| author | Finn Jochims Rebecca Strohm Claudia von Montfort Chantal-Kristin Wenzel Niklas Klahm Arun Kumar Kondadi Wilhelm Stahl Andreas S. Reichert Peter Brenneisen |
| author_facet | Finn Jochims Rebecca Strohm Claudia von Montfort Chantal-Kristin Wenzel Niklas Klahm Arun Kumar Kondadi Wilhelm Stahl Andreas S. Reichert Peter Brenneisen |
| author_sort | Finn Jochims |
| collection | DOAJ |
| description | Despite great efforts to develop new therapeutic strategies to combat melanoma, the prognosis remains rather poor. Artesunate (ART) is an antimalarial drug displaying anti-cancer effects in vitro and in vivo. In this in vitro study, we investigated the selectivity of ART on melanoma cells. Furthermore, we aimed to further elucidate the mechanism of the drug with a focus on the role of iron, the induction of oxidative stress and the implication of the enzyme heme oxygenase 1 (HO-1). ART treatment decreased the cell viability of A375 melanoma cells while it did not affect the viability of normal human dermal fibroblasts, used as a model for normal (healthy) cells. ART’s toxicity was shown to be dependent on intracellular iron and the drug induced high levels of oxidative stress as well as upregulation of HO-1. Melanoma cells deficient in HO-1 or treated with a HO-1 inhibitor were less sensitive towards ART. Taken together, our study demonstrates that ART induces oxidative stress resulting in the upregulation of HO-1 in melanoma cells, which subsequently triggers the effect of ART’s own toxicity. This new finding that HO-1 is involved in ART-mediated toxicity may open up new perspectives in cancer therapy. |
| first_indexed | 2024-03-10T23:00:11Z |
| format | Article |
| id | doaj.art-4fa7d1be0d614305af8b555387b4dd5c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:11Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4fa7d1be0d614305af8b555387b4dd5c2023-11-19T09:40:40ZengMDPI AGBiomedicines2227-90592023-08-01119239310.3390/biomedicines11092393The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma CellsFinn Jochims0Rebecca Strohm1Claudia von Montfort2Chantal-Kristin Wenzel3Niklas Klahm4Arun Kumar Kondadi5Wilhelm Stahl6Andreas S. Reichert7Peter Brenneisen8Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDespite great efforts to develop new therapeutic strategies to combat melanoma, the prognosis remains rather poor. Artesunate (ART) is an antimalarial drug displaying anti-cancer effects in vitro and in vivo. In this in vitro study, we investigated the selectivity of ART on melanoma cells. Furthermore, we aimed to further elucidate the mechanism of the drug with a focus on the role of iron, the induction of oxidative stress and the implication of the enzyme heme oxygenase 1 (HO-1). ART treatment decreased the cell viability of A375 melanoma cells while it did not affect the viability of normal human dermal fibroblasts, used as a model for normal (healthy) cells. ART’s toxicity was shown to be dependent on intracellular iron and the drug induced high levels of oxidative stress as well as upregulation of HO-1. Melanoma cells deficient in HO-1 or treated with a HO-1 inhibitor were less sensitive towards ART. Taken together, our study demonstrates that ART induces oxidative stress resulting in the upregulation of HO-1 in melanoma cells, which subsequently triggers the effect of ART’s own toxicity. This new finding that HO-1 is involved in ART-mediated toxicity may open up new perspectives in cancer therapy.https://www.mdpi.com/2227-9059/11/9/2393melanomacancer therapydrug repurposingoxidative stressnatural compoundartesunate |
| spellingShingle | Finn Jochims Rebecca Strohm Claudia von Montfort Chantal-Kristin Wenzel Niklas Klahm Arun Kumar Kondadi Wilhelm Stahl Andreas S. Reichert Peter Brenneisen The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells Biomedicines melanoma cancer therapy drug repurposing oxidative stress natural compound artesunate |
| title | The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells |
| title_full | The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells |
| title_fullStr | The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells |
| title_full_unstemmed | The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells |
| title_short | The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells |
| title_sort | antimalarial drug artesunate mediates selective cytotoxicity by upregulating ho 1 in melanoma cells |
| topic | melanoma cancer therapy drug repurposing oxidative stress natural compound artesunate |
| url | https://www.mdpi.com/2227-9059/11/9/2393 |
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