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Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Leukemia volume 16, pages 2285–2291 (2002)Cite this article

Abstract

PTPases are key signaling molecules and targets for developing novel therapeutics. We have studied the in vitro biological activity of PTPase inhibitor sodium stibogluconate (SS) on differentiation and proliferation of myeloid leukemia cell lines (NB4, HL-60 and U937). SS (250 μg/ml, 6 days) induced 87% of NB4 cells to reduce nitroblue tetrazolium (NBT), in comparison to the 90% induced by ATRA (1 μM, 6 days). SS treatment of NB4 cells resulted in an increase of CD11b expression and of a morphologically more mature population, coincident with growth arrest at S phase and increased cell death. The effect of SS on NB4 differentiation was irreversible and required continuous drug exposure. SS (400 μg/ml, 6 days) induced 60% and 55% of NBT-positive cells in HL-60 and U937 cell lines, which were augmented in the presence of GM-CSF (25 ng/ml) to levels (85% and 81%, respectively) comparable to those induced by ATRA. SS induced increased tyrosine phosphorylation of cellular proteins in the AML cell lines and inactivated SHP-1 PTPase in NB4 cells, consistent with SS functioning as a PTPase inhibitor in the leukemia cells. These results provide the first evidence of an anti-leukemia activity of SS as a PTPase inhibitor.

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Acknowledgements

The authors thank Mingli Cao for technical assistance, Dr R Ganapathi for providing ATRA and many colleagues for providing cell lines. This work is supported in part by grants R01CA79891 and R01MG58893 to T Yi.

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Authors and Affiliations

  1. Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA

    MK Pathak & T Yi

  2. Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH, USA

    T Yi

  3. Sichuan University, Chengdu, Sichuan, People's Republic of China

    X Hu

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Pathak, M., Hu, X. & Yi, T. Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro. Leukemia 16, 2285–2291 (2002). https://doi.org/10.1038/sj.leu.2402692

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