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30.09.2022 | original article

Polo-like kinase inhibitor BI2536 induces eryptosis

verfasst von: Dr. Mohamed Jemaà, Raja Mokdad Gargouri, Florian Lang

Erschienen in: Wiener Medizinische Wochenschrift

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Summary

BI2536 is potent inhibitor of polo-like kinases PLK1, 2, and 3. The inhibition of PLKs in nucleated cells induces apoptosis by perturbing the cell cycle with consequent engagement of mitotic catastrophe. BI2536 is being tested as chemotherapy in various phase I/II/III clinical trials. Erythrocytes do not have a nucleus; however, they may undergo programmed suicide with characteristic hallmarks including cell shrinkage and phosphatidylserine translocation to the cell surface. This particular death is baptized eryptosis. Our study explored whether BI2536 induces eryptosis. We used flow cytometry to access death in red blood cells. We analyzed the cellular volume, the intracellular calcium concentration, the cell surface phosphatidylserine exposure, and the ceramide abundance. In addition, we analyzed the effect of BI2536 on hemolysis. Our investigation showed that after 48 h of incubation with PLK inhibitor BI2536, erythrocytes lost volume and were positive for annexin‑V without any effect on hemolysis. Cells also showed an abundance of ceramide and an increase of intracellular calcium. All these finding suggest that BI2536 provokes eryptosis in red blood cells, ostensibly in part due to Ca2+ entry and ceramide accumulation.
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Metadaten
Titel
Polo-like kinase inhibitor BI2536 induces eryptosis
verfasst von
Dr. Mohamed Jemaà
Raja Mokdad Gargouri
Florian Lang
Publikationsdatum
30.09.2022
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-022-00966-7