5-Aza-2'-deoxycytidine enhances differentiation and apoptosis induced by phenylbutyrate in Kasumi-1 cells.
- Author:
Chang-lai HAO
1
;
Ke-jing TANG
;
Sen CHEN
;
Hai-yan XING
;
Min WANG
;
Jian-xiang WANG
Author Information
- Publication Type:Journal Article
- MeSH: Acute Disease; Apoptosis; drug effects; Azacitidine; administration & dosage; analogs & derivatives; pharmacology; CD11b Antigen; metabolism; CD13 Antigens; metabolism; Cell Cycle; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; Dose-Response Relationship, Drug; Drug Synergism; Humans; Leukemia, Myeloid; immunology; pathology; Phenylbutyrates; pharmacology
- From: Chinese Journal of Oncology 2005;27(3):148-151
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSKasumi-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.
RESULTSTreatment 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.
CONCLUSIONPhenylbuty rate, when combined with 5-Aza-CdR, inhibits AML cell in vitro proliferation and increases apoptosis in a synergistic fashion.