Requirement of caspase-3(-like) protease-mediated hydrogen peroxide production for apoptosis induced by various anticancer drugs

Siro Simizu, Minoru Takada, Kazuo Umezawa, Masaya Imoto

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Caspase-3(-like) proteases play important roles in controlling mammalian apoptosis. However, the downstream events from the caspase-3(-like) protease activation to death of cells are still unclear. Previously, we reported that hydrogen peroxide (H2O2) was generated by the activation of caspase-3(- like) proteases in the process of tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma Ms-1 cells. In the present study, we examined whether generation of H2O2 is a critical event for the apoptotic pathway downstream of caspase-3(-like) protease activation by various anticancer drugs. Anticancer drugs such as camptothecin, vinblastine, inostamycin, and adriamycin induced activation of caspase-3(-like) proteases and apoptosis. Generation of H2O2 was commonly detected after treatment with each of the four anticancer drugs, and scavenging of H2O2 caused cells to fail to undergo apoptosis. Moreover, anticancer drug-induced H2O2 production was inhibited not only by an inhibitor of caspase-3(-like) proteases but also by diphenyleneiodonium chloride, an inhibitor of flavonoid-containing enzymes such as NADPH oxidase. However, activation of caspase-3(-like) proteases was not inhibited by diphenyleneiodonium chloride. These findings suggest that activation of caspase-3(-like) proteases by various anticancer drugs causes generation of H2O2 presumably through the activation of NADPH oxidase, thereby inducing apoptosis. Therefore, H2O2 may function as a common mediator for apoptosis induced by various anticancer drugs.

Original languageEnglish
Pages (from-to)26900-26907
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number41
DOIs
Publication statusPublished - 1998 Oct 9

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Caspase 3
Hydrogen Peroxide
Peptide Hydrolases
Apoptosis
Chemical activation
Pharmaceutical Preparations
NADPH Oxidase
Cells
Camptothecin
Vinblastine
Scavenging
Small Cell Lung Carcinoma
Flavonoids
Protein-Tyrosine Kinases
Doxorubicin
Cell Death
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Requirement of caspase-3(-like) protease-mediated hydrogen peroxide production for apoptosis induced by various anticancer drugs. / Simizu, Siro; Takada, Minoru; Umezawa, Kazuo; Imoto, Masaya.

In: Journal of Biological Chemistry, Vol. 273, No. 41, 09.10.1998, p. 26900-26907.

Research output: Contribution to journalArticle

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