Effects of the combination of decitabine and homoharringtonine in SKM-1 and Kg-1a cells.

Abstract:

:The methylation inhibitor decitabine (DAC) has great therapeutic value for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, DAC monotherapy is associated with relatively low rates of overall response and complete remission. Previous studies have shown promising results for combination treatment regimens including DAC. Homoharringtonine (HHT), an alkaloid from Chinese natural plants and Cephalotaxus, has demonstrated potential for leukemia treatment. Our studies have suggested that the combination of DAC and HHT has synergistic effects for inhibiting the viability of SKM-1 and Kg-1a cells. This combination leads to enhanced inhibition of colony formation and apoptosis induction compared with DAC alone in SKM-1 but not Kg-1a cells. Only high-dose DAC and HHT significantly up-regulate caspase-3 and caspase-9 and inhibit BCL-XL in the SKM-1 cell line. The combined effects of DAC plus HHT on apoptosis may not only depend on regulation of the apoptosis-related genes we examined but others as well. HHT had no demethylation effects, and HHT in combination with DAC had no enhanced effects on hypomethylation and DNMT1, DNMT3A and DNMT3B mRNA expression in SKM-1 cells. Overall, these results suggest that DAC used in combination with HHT may have clinical potential for MDS treatment.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Geng S,Yao H,Weng J,Tong J,Huang X,Wu P,Deng C,Li M,Lu Z,Du X

doi

10.1016/j.leukres.2016.02.002

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

17-24

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(16)30017-0

journal_volume

44

pub_type

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