Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: Effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis

Binet, François; Cavalli, Hélène; Moisan, Eliane et Girard, Denis ORCID: https://orcid.org/0000-0002-3342-5027 (2006). Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: Effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis British Journal of Haematology , vol. 132 , nº 3. pp. 349-358. DOI: 10.1111/j.1365-2141.2005.05866.x.

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Résumé

The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

Type de document:	Article
Mots-clés libres:	neutrophils, caspases, reactive oxygen species, de novo protein synthesis.
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	22 oct. 2024 13:23
Dernière modification:	22 oct. 2024 13:23
URI:	https://espace.inrs.ca/id/eprint/14415

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