5-Aza-2'-deoxycytidine enhances differentiation and apoptosis induced by phenylbutyrate in Kasumi-1 cells
Hao, C-lai.; Tang, K-jing.; Chen, S.; Xing, H-yan.; Wang, M.; Wang, J-xiang.
Zhonghua Zhong Liu Za Zhi 27(3): 148-151
2005
ISSN/ISBN: 0253-3766 PMID: 15946563 Document Number: 592241
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 IC50 of 2.3 mmol/L. When combined with 5-Aza-CdR PB resulted in a greater growth inhibition with an IC50 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. Conclusion Phenylbutyrate, when combined with 5-Aza-CdR, inhibits AML cell in vitro proliferation and increases apoptosis in a synergistic fashion.