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.

中文翻译：

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Zebularine诱导的骨髓瘤细胞死亡伴随c-Myc表达降低。

目的

表观遗传疗法已被证明在几种血液系统恶性肿瘤中临床有效。在这里，我们旨在评估第二代DNA脱甲基剂zebularine对多发性骨髓瘤（MM）的影响。

方法

Western blot，ELISA，qRT-PCR，增殖测定和细胞转染用于研究zebularine在MM中的作用机制。

结果

我们发现zebularine在大多数测试的MM细胞系中诱导凋亡和DNA去甲基化。其细胞毒性作用与c-Myc蛋白水平的时间依赖性降低有关。此外，在8个测试的MM细胞系中有5个，zebularine诱导了H2AX磷酸化，这是DNA损伤的替代标志。

结论

我们的研究揭示了zebularine对MM的新作用，这可能会对基于DNA甲基化的疗法产生潜在影响。