Arsenic disulfide-triggered apoptosis and erythroid differentiation in myelodysplastic syndrome and acute myeloid leukemia cell lines. Issue 6 (September 2014)

• Record Type: Journal Article
• Authors: Hu, Xiao-Mei; Yuan, Bo; Tanaka, Sachiko; Song, Min-Min; Onda, Kenji; Tohyama, Kaoru; Zhou, Ai-Xiang; Toyoda, Hiroo; Hirano, Toshihiko
• Is Part Of: Hematology. Volume 19:Issue 6(2014)
• Page Start: 352
• Page End: 360
• Publication Date: 2014-09
• Subjects: Blood -- Diseases -- Periodicals; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; 616.15005
• DOI: 10.1179/1607845413Y.0000000138
• Languages: English
• ISSNs: 1024-5332

Abstract

<abstract> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <sec> <title>Objectives</title> <p>Effects of arsenic disulfide (As<sub>2</sub>S<sub>2</sub>) 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 <italic>de novo</italic> AML, respectively.</p> </sec> <sec> <title>Methods</title> <p>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.</p> </sec> <sec> <title>Results</title> <p>As<sub>2</sub>S<sub>2</sub> inhibited cell growth of these cell lines. Of note, the IC<sub>50</sub> value of As<sub>2</sub>S<sub>2</sub> 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<sub>2</sub>S<sub>2</sub> for 72 hours. However, similar phenomena were only observed in HL-60 cells when treated with as high as 16 µM As<sub>2</sub>S<sub>2</sub>. Furthermore, As<sub>2</sub>S<sub>2</sub> 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<sub>2</sub>S<sub>2</sub>-induced erythroid differentiation was observed in HL-60 cells. Treatment with relatively high concentration of As<sub>2</sub>S<sub>2</sub> resulted in the downregulation of Bcl-2 and Bid proteins in HL-60 cells.</p> </sec> <sec> <title>Discussion</title> <p>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<sub>2</sub>S<sub>2</sub>, but also its cytotoxicity associated with apoptosis induction. These findings further provide novel insight into As<sub>2</sub>S<sub>2</sub> action toward its use for clinical application in patients with hematological disorders.</p> </sec> </abstract>