Induction of hydrogen peroxide production and bax expression by caspase- 3(-like) proteases in tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma cells

Siro Simizu, Kazuo Umezawa, Minoru Takada, Nadir Arber, Masaya Imoto

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Abstract

In our previous studies (S. Simizu, et al., 1996, Cancer Res. 56, 4978- 4982), we reported that apoptosis of human small cell lung carcinoma (SCLC) cells induced by protein tyrosine kinase inhibitors, such as erbstatin and herbimycin A, was mediated by H2O2 via a newly synthesized protein(s). In the present study, we demonstrated that induction of apoptosis by erbstatin resulted in activation of caspase-3(like) proteases, which are interleukin- 1β-converting enzyme family proteases (caspases) and that inhibition of these protease activities reduced the extent of cell death and H2O2 generation. We also demonstrated that expression of apoptotic protein Bax was induced by erbstatin. Erbstatin-induced Bax expression was inhibited by the inhibitor of caspase-3(-like) proteases. These results indicate that generation of intracellular H2O2 and Bax expression in tyrosine kinase inhibitor-induced apoptosis were modulated by the activation of caspase-3-(- like) proteases in SCLC cells.

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalExperimental Cell Research
Volume238
Issue number1
DOIs
Publication statusPublished - 1998 Jan 10

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Small Cell Lung Carcinoma
Caspase 3
Protein-Tyrosine Kinases
Hydrogen Peroxide
Peptide Hydrolases
Apoptosis
bcl-2-Associated X Protein
Caspase 1
Protein Kinase Inhibitors
Caspases
Cell Death
erbstatin
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

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abstract = "In our previous studies (S. Simizu, et al., 1996, Cancer Res. 56, 4978- 4982), we reported that apoptosis of human small cell lung carcinoma (SCLC) cells induced by protein tyrosine kinase inhibitors, such as erbstatin and herbimycin A, was mediated by H2O2 via a newly synthesized protein(s). In the present study, we demonstrated that induction of apoptosis by erbstatin resulted in activation of caspase-3(like) proteases, which are interleukin- 1β-converting enzyme family proteases (caspases) and that inhibition of these protease activities reduced the extent of cell death and H2O2 generation. We also demonstrated that expression of apoptotic protein Bax was induced by erbstatin. Erbstatin-induced Bax expression was inhibited by the inhibitor of caspase-3(-like) proteases. These results indicate that generation of intracellular H2O2 and Bax expression in tyrosine kinase inhibitor-induced apoptosis were modulated by the activation of caspase-3-(- like) proteases in SCLC cells.",
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T1 - Induction of hydrogen peroxide production and bax expression by caspase- 3(-like) proteases in tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma cells

AU - Simizu, Siro

AU - Umezawa, Kazuo

AU - Takada, Minoru

AU - Arber, Nadir

AU - Imoto, Masaya

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