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Differential responses to Bcl-2 family genes to etoposide in chronic myeloid leukemia K562 cells

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Abstract

Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.

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Authors and Affiliations

  1. Department of Oncology, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Sachiko Fukumi & Tsuneya Ohno

  2. Department of Oncology, Department of Internal Medicine (1) of Daisan Hospital, Japan

    Junko Horiguchi-Yamada

  3. Deparment of Internal Medicine (1) of Daisan Hospital, Japan

    Shuji Nakada & Makoto Nagari

  4. Department of Molecular Genetics, Department of Internal Medicine, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Hisashi Yamada

Authors
  1. Sachiko Fukumi
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  2. Junko Horiguchi-Yamada
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  3. Shuji Nakada
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  4. Makoto Nagari
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  5. Tsuneya Ohno
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  6. Hisashi Yamada
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Fukumi, S., Horiguchi-Yamada, J., Nakada, S. et al. Differential responses to Bcl-2 family genes to etoposide in chronic myeloid leukemia K562 cells. Mol Cell Biochem 206, 43–50 (2000). https://doi.org/10.1023/A:1007056727876

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