title: 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.
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Minming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Zesheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Hematology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China. Electronic address: miyadu@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D049109:Cell Proliferation / Q000187:drug effects*; D000077209:Decitabine; D006248:Harringtonines / Q000008:administration & dosage; D000077863:Homoharringtonine; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D006248:Harringtonines; D012333:RNA, Messenger; D000077863:Homoharringtonine; D000077209:Decitabine; D001374:Azacitidine
keywords: Apoptosis; Decitabine; Homoharringtonine; MDS; Methylation