A combination of low-dose decitabine and chidamide resulted in synergistic effects on the proliferation and apoptosis of human myeloid leukemia cell lines.

In this study, the combination of DAC at low doses and chidamide showed enhanced inhibition of myeloid leukemia cell (K562, THP-1) growth. As a novel HDACi, chidamide increased the level of ace-H3K18 expression. Combined use of low-dose DAC and chidamide arrested the cell cycle at the G0/G1 phase by upregulating p21 expression, and the combination also suppressed PI3K/AKT/mTOR signaling pathway. Furthermore, chidamide enhanced the apoptotic effect of DAC by downregulating expression of Bcl-2 and pro-caspase-3 and upregulating that of Bax, cleaved PARP-1, and caspase-9. Moreover, the mitochondrial transmembrane potential was significantly decreased in DAC-, chidamide-, or combination-treated leukemia cells. These results suggest that targeting the leukemia epigenome through the combination of low-dose DAC and chidamide is a promising approach.
PMID: 31934307 [PubMed]

Source: American Journal of Translational Research - January 16, 2020 Category: Research Tags: Am J Transl Res Source Type: research