The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody.

Détails

ID Serval
serval:BIB_8DB096080B48
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody.
Périodique
Leukemia and Lymphoma
Auteur⸱e⸱s
Nahimana A., Aubry D., Breton C.S., Majjigapu S.R., Sordat B., Vogel P., Duchosal M.A.
ISSN
1029-2403 (Electronic)
ISSN-L
1026-8022
Statut éditorial
Publié
Date de publication
2014
Volume
55
Numéro
9
Pages
2141-2150
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Abstract APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis that exhibits potent anti-lymphoma activity. Rituximab (RTX), an anti-CD20 antibody, kills lymphoma cells by direct apoptosis and antibody- and complement-dependent cell-mediated cytotoxicities, and has clinical efficacy in non-Hodgkin cell lymphomas. In the present study, we evaluated whether RTX could potentiate APO866-induced human B-lymphoma cell death and shed light on death-mediated mechanisms associated with this drug combination. We found that RTX significantly increases APO866-induced death in lymphoma cells from patients and lines. Mechanisms include enhancement of autophagy-mediated cell death, activation of caspase 3 and exacerbation of mitochondrial depolarization, but not increase of reactive oxygen species (ROS) production, when compared with those induced by each drug alone. In vivo, combined administration of APO866 with RTX in a laboratory model of human aggressive lymphoma significantly decreased tumor burden and prolonged survival over single-agent treatment. Our study demonstrates that the combination of RTX and APO866 optimizes B-cell lymphoma apoptosis and therapeutic efficacy over both compounds administered separately.
Pubmed
Web of science
Création de la notice
04/02/2014 11:43
Dernière modification de la notice
20/08/2019 15:51
Données d'usage