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Annals of Hematology
Published in: Annals of Hematology 6/2012

01-06-2012 | Original Article

The proteasome inhibitor bortezomib targets cell cycle and apoptosis and acts synergistically in a sequence-dependent way with chemotherapeutic agents in mantle cell lymphoma

Authors: Grit Hutter, Malte Rieken, Alessandro Pastore, Oliver Weigert, Yvonne Zimmermann, Marc Weinkauf, Wolfgang Hiddemann, Martin Dreyling

Published in: Annals of Hematology | Issue 6/2012

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Abstract

Single-agent bortezomib, a potent, selective, and reversible inhibitor of the 26S proteasome, has demonstrated clinical efficacy in relapsed and refractory mantle cell lymphoma (MCL). Objective response is achieved in up to 45% of the MCL patients; however, complete remission rates are low and duration of response proved to be relatively short. These limitations may be overcome by combining proteasome inhibition with conventional chemotherapy. Rational combination treatment and schedules require profound knowledge of underlying molecular mechanisms. Here we show that single-agent bortezomib treatment of MCL cell lines leads to G2/M arrest and induction of apoptosis accompanied by downregulation of EIF4E and CCND1 mRNA but upregulation of p15(INK4B) and p21 mRNA. We further present synergistic efficacy of bortezomib combined with cytarabine in MCL cell lines. Interestingly this sequence-dependent synergistic effect was seen almost exclusively in combination with AraC, indicating that pretreatment with cytarabine, followed by proteasome inhibition, may be the preferred approach.
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Metadata
Title
The proteasome inhibitor bortezomib targets cell cycle and apoptosis and acts synergistically in a sequence-dependent way with chemotherapeutic agents in mantle cell lymphoma
Authors
Grit Hutter
Malte Rieken
Alessandro Pastore
Oliver Weigert
Yvonne Zimmermann
Marc Weinkauf
Wolfgang Hiddemann
Martin Dreyling
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 6/2012
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-011-1377-y

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