000202385 001__ 202385
000202385 005__ 20181203023631.0
000202385 0247_ $$2doi$$a10.3109/10428194.2013.869325
000202385 022__ $$a1042-8194
000202385 02470 $$2ISI$$a000340460200028
000202385 037__ $$aARTICLE
000202385 245__ $$aThe anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody
000202385 260__ $$bInforma Healthcare$$c2014$$aLondon
000202385 269__ $$a2014
000202385 300__ $$a10
000202385 336__ $$aJournal Articles
000202385 520__ $$aAPO866 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.
000202385 6531_ $$aRTX
000202385 6531_ $$aAPO866
000202385 6531_ $$aFK866
000202385 6531_ $$alymphoma
000202385 6531_ $$aleukemia
000202385 6531_ $$atherapy
000202385 700__ $$uUniv Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland$$aNahimana, Aimable
000202385 700__ $$uUniv Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland$$aAubry, Dominique
000202385 700__ $$uUniv Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland$$aBreton, Caroline S.
000202385 700__ $$0242651$$g192493$$aMajjigapu, Somi R.
000202385 700__ $$aSordat, Bernard
000202385 700__ $$0240222$$g123681$$aVogel, Pierre
000202385 700__ $$aDuchosal, Michel A.$$uUniv Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland
000202385 773__ $$j55$$tLeukemia & Lymphoma$$k9$$q2141-2150
000202385 909C0 $$xU10111$$0252076$$pLGSA
000202385 909CO $$pSB$$particle$$ooai:infoscience.tind.io:202385
000202385 937__ $$aEPFL-ARTICLE-202385
000202385 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000202385 980__ $$aARTICLE