Erschienen in:
11.05.2020 | Report
Zebularine-induced myeloma cell death is accompanied by decreased c-Myc expression
verfasst von:
Patryk Krzeminski, Ramón García-Sanz, Norma C. Gutiérrez
Erschienen in:
Cellular Oncology
|
Ausgabe 4/2020
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Abstract
Purpose
Epigenetic therapies have proven to be clinically effective in several hematological malignancies. Here, we aimed to evaluate the effect of a second-generation DNA demethylation agent, zebularine, on multiple myeloma (MM).
Methods
Western blot, ELISA, qRT-PCR, proliferation assays and cell transfection were used to investigate the mechanism of action of zebularine in MM.
Results
We found that zebularine induced apoptosis and DNA demethylation in most of the MM cell lines tested. Its cytotoxic effect was associated with a time-dependent decrease in the level of c-Myc protein. Moreover, zebularine induced H2AX phosphorylation, a surrogate marker of DNA damage, in five out of eight MM cell lines tested.
Conclusions
Our study revealed novel effects of zebularine on MM that may have potential implications for DNA methylation-based therapies.