[5-Aza-2'-deoxycytidine enhances differentiation and apoptosis induced by phenylbutyrate in Kasumi-1 cells].
OBJECTIVE
To investigate whether phenylbutyrate (PB) combined with 5-aza-2'-deoxycytidine (5-Aza-CdR)could inhibit transcription repression and induce t(8;21) acute myelogenous leukemia (AML) Kasumi-1 cells to differentiate and undergo apoptosis.


METHODS
Kasumi-1 cells were treated with PB and 5-Aza-CdR at different concentrations in suspension culture. Cellular proliferation was determined by the MTT assay, expression of myeloid-specific differentiation antigen and cell cycles were analyzed by flow cytometry. Cell apoptosis were assessed using AnnexinV/PI staining and flow cytometry.


RESULTS
Treatment of Kasumi-1 cells with PB caused a dose-dependent inhibition of proliferation, with an IC(50) of 2.3 mmol/L. When combined with 5-Aza-CdR, PB resulted in a greater growth inhibition with an IC(50) of 1.95 mmol/L. Treatment of Kasumi-1 cells with PB resulted in cell cycle arrest at G(0)/G(1), while combined treatment with PB and 5-Aza-CdR led to cell cycle arrest at G(2)/M. Expression of myeloid cell differentiation antigens CD11b and CD13 induced by PB was enhanced when Kasumi-1 cells were pretreated with low dose of 5-Aza-CdR. High, but not low, concentrations of 5-Aza-CdR could enhance early apoptosis of Kasumi-1 cells induced by PB.


CONCLUSIONS
Phenylbuty rate, when combined with 5-Aza-CdR, inhibits AML cell in vitro proliferation and increases apoptosis in a synergistic fashion.
Hao
Chang-lai
CL
Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, China.
Tang
Ke-jing
KJ
Chen
Sen
S
Xing
Hai-yan
HY
Wang
Min
M
Wang
Jian-xiang
JX
D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D010654:Phenylbutyrates / Q000494:pharmacology*
D039481:CD11b Antigen; D010654:Phenylbutyrates; D000077209:Decitabine; D018826:CD13 Antigens; D001374:Azacitidine