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KMID : 0366220050400020093
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Korean Journal of Hematology
2005 Volume.40 No. 2 p.93 ~ p.100
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Arsenic Trioxide Induces Erythroid Differentiation and Apoptosis of ATRA Resistant K562 Human Leukemia Cells Through the Down-Regulation of Bcl-2
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You Yong-Kyu
Jung Hee-Jung
Won Jong-Ho
Kim Sook-Ja
Bae Sang-Byung
Kim Chan-Kyu
Lee Nam-Su
Park Hee-Sook
Lee Kyu-Taek
Park Sung-Kyu
Hong Dae-Sik
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Abstract
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Background: Arsenic trioxide (As2O3) has been identified as an effective drug for the treatment of acute promyelocytic leukemia (APL). However, the role of As2O3 during the erythroid differentiation of human leukemic cells remains unknown. In this study, we investigated the in vitro effects of As2O3 on the erythroid differentiation of K562 cell line and on the expressions and regulations of the apoptotic modulators of this process.
Methods: The K562 cells were cultured in the presence of 0.1, 0.5 and 1.0μM As2O3, or 1.0 and 10μM all trans retinoic acid (ATRA). The expression of glycophorin A before and after treatment with As2O3 or ATRA in K562 cells was assessed by flow cytometry and western blot. The expression of Bcl-2 and caspase-3 were determined by western blot.
Results: The viability of K562 cells was not decreased after treating with 0.1 and 0.5μM of As2O3 but was significantly reduced at a dose of 1.0μM. Caspase 3 activation was not observed at 0.1 and 0.5μM of As2O3 until 12 days, but was activated by 1.0μM of As2O3 from day 3. The expression of glycophorin A was increased in dose dependent manner by As2O3 treatment but was not changed in ATRA treated K562 cells. The expression of Bcl-2 was increased by 0.1 and 0.5μM of As2O3 but was reduced abruptly by 1.0μM of As2O3.
Conclusion: These results suggest that As2O3 induces the erythroid differentiation of K562 cells and that 1.0 μM of As2O3 induces apoptosis through the down-regulation of Bcl-2.
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KEYWORD
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Arsenic trioxide, Differentiation, Apoptosis, ATRA, K562
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