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Sustained activation of c-jun-terminal kinase (JNK) is closely related to arsenic trioxide-induced apoptosis in an acute myeloid leukemia (M2)-derived cell line, NKM-1

Leukemia volume 17, pages 2189–2195 (2003)Cite this article

Abstract

High concentrations (greater than 5 μ M) of arsenic trioxide (As2O3) have been reported to be able to induce apoptosis in several malignant cells. We explored cell lines in which apoptosis was induced with a therapeutic concentration (1–2 μ M) of As2O3, and found that 1 μ M of As2O3 induced apoptosis in the NKM-1 cell line, which was established from a patient with acute myeloid leukemia (M2). Apoptosis induced by 1 μ M of As2O3 in NKM-1 cells was accompanied by an increased cellular content of H2O2, a decreased mitochondrial membrane potential (Δψm), and activation of caspase-3. C-Jun-terminal kinase (JNK) was activated only in NKM-1 cells and arsenic-sensitive NB4 cells, but not in arsenic-insensitive HL-60 cells. Activation of JNK in NKM-1 was sustained from 6 to 24 h after As2O3 treatment, and preceded changes in cellular H2O2, Δψm, and caspase-3 activation. Moreover, addition of a JNK inhibitor reduced the percentage of apoptotic cells after the As2O3 treatment. Taken together, in the M2 cell line NKM-1, 1 μ M of As2O3 induced sustained activation of JNK and apoptosis. This finding may provide a basis to select a subgroup other than acute promyelocytic leukemia, which can benefit from As2O3 treatment.

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Acknowledgements

We thank Satoshi Suzuki and Chika Wakamatsu for their excellent technical assistance.

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Authors and Affiliations

  1. The First Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

    T Kajiguchi, K Yamamoto, T Naoe & N Emi

  2. Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    K Hossain, A A Akhand & I Nakashima

  3. Nagoya National Hospital, Nagoya, Japan

    H Saito

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Kajiguchi, T., Yamamoto, K., Hossain, K. et al. Sustained activation of c-jun-terminal kinase (JNK) is closely related to arsenic trioxide-induced apoptosis in an acute myeloid leukemia (M2)-derived cell line, NKM-1. Leukemia 17, 2189–2195 (2003). https://doi.org/10.1038/sj.leu.2403120

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