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Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent myelodysplastic syndrome-progressed leukemia cell line F-36p with complex karyotype including monosomy 7

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Abstract

Objective

Acute myeloid leukemia progressed from myelodysplastic syndrome (MDS/AML) is generally incurable with poor prognosis for complex karyotype including monosomy 7 (-7). Qinghuang Powder (青黄散, QHP), which includes Qing Dai (Indigo naturalis) and Xiong Huang (realgar) in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains > 90% arsenic disulfide (As2S2). F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells.

Methods

Cell proliferation was measured by an 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide (PI) exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a (GpA).

Results

After treatment with As2S2 at concentrations of 0.5 to 16 μmol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations (IC50) of As2S2 against the proliferation of F-36p cells was 6 μmol/L. The apoptotic cells significantly increased in a dose-dependent mannar (P<0.05). The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner (P<0.05). Significant increases of CD235a-positive cells were concurrently observed (P<0.05) also in a dose-dependent manner.

Conclusions

As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7. The data suggest that QHP and/or As2S2 could be a potential candidate in the treatment of MDS or MDS/AML even with unfavorable cytogenetics.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan

    Xiao-mei Hu  (胡晓梅), Sachiko Tanaka, Kenji Onda & Toshihiko Hirano

  2. Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan

    Bo Yuan  (袁 博) & Hiroo Toyoda

  3. National Therapeutic Center of Hematology of Traditional Chinese Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China

    Xiao-mei Hu  (胡晓梅), Rou Ma  (麻 柔) & Feng Liu  (刘 峰)

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  1. Xiao-mei Hu  (胡晓梅)
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  2. Sachiko Tanaka
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  3. Kenji Onda
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  4. Bo Yuan  (袁 博)
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  6. Rou Ma  (麻 柔)
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  7. Feng Liu  (刘 峰)
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  8. Toshihiko Hirano
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Correspondence to Toshihiko Hirano.

Additional information

Supported in part by grants from Japan China Medical Association to Bo Yuan and XiaoMei Hu

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Hu, Xm., Tanaka, S., Onda, K. et al. Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent myelodysplastic syndrome-progressed leukemia cell line F-36p with complex karyotype including monosomy 7. Chin. J. Integr. Med. 20, 387–393 (2014). https://doi.org/10.1007/s11655-013-1514-7

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  • DOI: https://doi.org/10.1007/s11655-013-1514-7

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