Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells.

ABSTRACT: EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines. GSK126 induced massive apoptosis in MM.1S, LP1 and RPMI8226 cells. Progressive release of mitochondrial cytochrome c and AIF into the cytosol was detected in GSK126-treated MM cells. GSK126 treatment elicited caspase-3-dependent MCL-1

SUBMITTER: Zeng D 

PROVIDER: S-EPMC5356890 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature