Role of endogenous regucalcin in protein tyrosine phosphatase regulation in the cloned rat hepatoma cells (H4-II-E) |
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Authors: | Inagaki Shyuichiroh Misawa Hiroyuki Yamaguchi Masayoshi |
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Institution: | (1) Department of Oncology, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan;(2) Department of Oncology, Department of Internal Medicine (1) of Daisan Hospital, Japan;(3) Deparment of Internal Medicine (1) of Daisan Hospital, Japan;(4) Department of Molecular Genetics, Department of Internal Medicine, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan |
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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 M) or high (100 M) 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 M 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 M 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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Keywords: | etoposide Bcl-XL Bax apoptosis K562 cells |
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