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Hu, Xiao-Mei; Yuan, Bo; Tanaka, Sachiko; Song, Min-Min; Onda, Kenji; Tohyama, Kaoru; Zhou, Ai-Xiang; Toyoda, Hiroo; Hirano, Toshihiko
Hematology (Luxembourg), 09/2014, Volume: 19, Issue: 6Journal Article
Objectives Effects of arsenic disulfide (As 2 S 2 ) were investigated by focusing on growth inhibition, apoptosis induction, and erythroid differentiation in MDS-L, F-36p and HL-60 cells, derived from myelodysplastic syndrome (MDS), MDS/acute myeloid leukemia (AML), and de novo AML, respectively. Methods Cell viability was determined by MTT assay. Apoptosis induction was analyzed using Annexin V/propidium iodide staining. Erythroid differentiation was assessed by the expression level of CD235a, a marker for detection of the erythroid cell lineage. The activation of p38 MAPK and the expression profile of apoptosis-related proteins Bcl-2 and Bid were analyzed using western blot. Results As 2 S 2 inhibited cell growth of these cell lines. Of note, the IC 50 value of As 2 S 2 in MDS-L cells was comparable to that in F-36p cells, and was half of that in HL-60 cells. A dose-dependent decrease in cell viability and concomitant increase in the percentage of apoptotic cells were observed in F-36p cells treated with 8 and 16 µM As 2 S 2 for 72 hours. However, similar phenomena were only observed in HL-60 cells when treated with as high as 16 µM As 2 S 2 . Furthermore, As 2 S 2 exerted more potent erythroid differentiation-inducing activity on F-36p cells than HL-60 cells. Interestingly, negative correlation between p38 MAPK signaling pathway and As 2 S 2 -induced erythroid differentiation was observed in HL-60 cells. Treatment with relatively high concentration of As 2 S 2 resulted in the downregulation of Bcl-2 and Bid proteins in HL-60 cells. Discussion These results suggest that compared to AML cell line, MDS and MDS/AML cell lines are more sensitive to not only the erythroid differentiation-inducing activity of As 2 S 2 , but also its cytotoxicity associated with apoptosis induction. These findings further provide novel insight into As 2 S 2 action toward its use for clinical application in patients with hematological disorders.
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