Zebularine-induced myeloma cell death is accompanied by decreased c-Myc expression.

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.

• Authors: Patryk Krzeminski, Ramón García-Sanz, Norma C Gutiérrez
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 43 Issue 4 Pg. 743-750 (Aug 2020) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 32394351 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• Cytidine
• pyrimidin-2-one beta-ribofuranoside

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytidine (analogs & derivatives, pharmacology)
• DNA Methylation (drug effects)
• Humans
• Multiple Myeloma
• Proto-Oncogene Proteins c-myc (metabolism)