Work

Arsenic Trioxide Induces Erythroid Differentiation and Apoptosis of K562 Human Leukemia Cells through the Down-Regulation of Bcl-2

Year: 2005

Type: article

Abstract: Background: Arsenic trioxide (As 2 O 3 ) has been identified as an effective drug for the treatment of acute promyelocytic leukemia (APL).However, the role of As 2 O 3 during the erythroid differentiation of human leukemic cells remains unknown.In this study, we investigated the in vitro effects of As 2 O 3 on the erythroid differentiation of the K562 cell line and also on the expression and regulation of the apoptotic modulators of this process.Methods: The K562 cells were cultured in the presence of 0.1, 0.5 and 1.0μMAs 2 O 3 , or they were cultured in the presence of 1.0 and 10μM all trans retinoic acid (ATRA).The expression of glycophorin A before and after treatment with As 2 O 3 or with ATRA in the K562 cells was assessed by flow cytometry and western blotting.The expressions of Bcl-2 and caspase-3 were determined by western blotting. Results:The viability of the K562 cells was not decreased after treating with 0.1 and 0.5μM of As 2 O 3 , but the viability was significantly reduced at a dose of 1.0μM.Caspase 3 activation was not observed at 0.1 and 0.5μM of As 2 O 3 until 12 days, but Caspase 3 was activated by 1.0μM of As 2 O 3 from day 3.The expression of glycophorin A was increased in dose dependent manner by As 2 O 3 treatment, but this was not changed in the ATRA treated K562 cells.The expression of Bcl-2 was increased by 0.1 and 0.5μM of As 2 O 3 , but it was abruptly reduced by 1.0μM of As 2 O 3 .Conclusion: These results suggest that As 2 O 3 induces the erythroid differentiation of K562 cells and that 1.0μM of As 2 O 3 induces apoptosis through the down-regulation of Bcl-2.(Korean J Hematol 2005; 40:93-100.)

Source: The Korean Journal of Hematology

DOI: 10.5045/kjh.2005.40.2.93