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

Details

Serval ID
serval:BIB_8DB096080B48
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody.
Journal
Leukemia and Lymphoma
Author(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
Publication state
Published
Issued date
2014
Volume
55
Number
9
Pages
2141-2150
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
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
Create date
04/02/2014 10:43
Last modification date
20/08/2019 14:51
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