Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells

Wakako Hiraoka, Nancy Vazquez, Wilberto Nieves-Neira, Stephen J. Chanock, Yves Pommier*

*Corresponding author for this work

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

We have used a human leukemia cell line that, after homologous recombination knockout of the gp91-phox subunit of the phagocyte respiratory- burst oxidase cytochrome b-558, mimics chronic granulomatous disease (X-CGD) to study the role of oxygen radicals in apoptosis. Camptothecin (CPT), a topoisomerase I inhibitor, induced significantly more apoptosis in PLB-985 cells than in X-CGD cells. Sensitivity to CPT was enhanced after neutrophilic differentiation, but was lost after monocytic differentiation. No difference between the two cell lines was observed after treatment with other apoptosis inducers, including etoposide, ultraviolet radiation, ionizing radiation, hydrogen peroxide, or 7-hydroxy-staurosporine. After granulocytic differentiation of both cell lines, CPT still induced apoptosis, suggesting independence from replication in fully differentiated and growth-arrested cells. Pyrrolidine dithiocarbamate (an antioxidant inhibitor of NF-κB) and catalase partially inhibited CPT-induced DNA fragmentation in granulocytic- differentiated PLB-985 cells, but had no effect in X-CGD cells. Flow cytometry analysis revealed that reactive oxygen intermediates were generated in CPT-treated PLB-985 cells. These data indicate that oxygen radicals generated by NADPH oxidase may contribute directly or indirectly to CPT- induced apoptosis in human leukemia and in neutrophilic-differentiated cells.

Original languageEnglish (US)
Pages (from-to)1961-1968
Number of pages8
JournalJournal of Clinical Investigation
Volume102
Issue number11
DOIs
StatePublished - Dec 1 1998

Keywords

  • Apoptosis
  • Camptothecin
  • Chronic granulomatous disease
  • NADPH oxidase
  • Reactive oxygen intermediates

ASJC Scopus subject areas

  • Medicine(all)

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