Artesunate affects T antigen expression and survival of virus-positive Merkel cell carcinoma
Please always quote using this URN: urn:nbn:de:bvb:20-opus-203851
- Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate — a drug used to treat malaria — has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival ofMerkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate — a drug used to treat malaria — has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival of MCPyV-positive MCC cells in vitro. This effect was accompanied by reduced large T antigen (LT) expression. Notably, however, it was even more efficient than shRNA-mediated downregulation of LT expression. Interestingly, in one MCC cell line (WaGa), T antigen knockdown rendered cells less sensitive to artesunate, while for two other MCC cell lines, we could not substantiate such a relation. Mechanistically, artesunate predominantly induces ferroptosis in MCPyV-positive MCC cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and β-mercaptoethanol reduced artesunate-induced death. Finally, application of artesunate in xenotransplanted mice demonstrated that growth of established MCC tumors can be significantly suppressed in vivo. In conclusion, our results revealed a highly anti-proliferative effect of the approved and generally well-tolerated anti-malaria compound artesunate on MCPyV-positive MCC cells, suggesting its potential usage for MCC therapy.…
Author: | Bhavishya Sarma, Christoph Willmes, Laura Angerer, Christian Adam, Jürgen C. Becker, Thibault Kervarrec, David Schrama, Roland Houben |
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URN: | urn:nbn:de:bvb:20-opus-203851 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie |
Language: | English |
Parent Title (English): | Cancers |
ISSN: | 2072-6694 |
Year of Completion: | 2020 |
Volume: | 12 |
Issue: | 4 |
Article Number: | 919 |
Source: | Cancers (2020) 12:4, 919. https://doi.org/10.3390/cancers12040919 |
DOI: | https://doi.org/10.3390/cancers12040919 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | MCC; Merkel cell carcinoma; artesunate; ferroptosis; polyomavirus |
Release Date: | 2022/05/24 |
Date of first Publication: | 2020/04/09 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |