| Autor: |
Dell'Anno, Irene, Martin, Sarah A., Barbarino, Marcella, Melani, Alessandra, Silvestri, Roberto, Bottaro, Maria, Paolicchi, Elisa, Corrado, Alda, Cipollini, Monica, Melaiu, Ombretta, Giordano, Antonio, Luzzi, Luca, Gemignani, Federica, Landi, Stefano |
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| Zdroj: |
Investigational New Drugs; Jun2021, Vol. 39 Issue 3, p644-657, 14p |
| Abstrakt: |
Summary: Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future "drug repositioning" approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. Results Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). Conclusion This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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