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Investigational New Drugs
Published in: Investigational New Drugs 2/2012

01-04-2012 | PRECLINICAL STUDIES

In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and lenalidomide against different cell lines

Authors: Martin Schmidt-Hieber, Robert Dabrowski, Andreas Weimann, Babette Aicher, Philipp Lohneis, Antonia Busse, Eckhard Thiel, Igor W. Blau

Published in: Investigational New Drugs | Issue 2/2012

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Summary

The novel AKT inhibitor perifosine, a synthetic alkylphospholipid, is currently being investigated in clinical trials for the treatment of different hematological and oncological malignancies. The in vitro cytotoxicity of perifosine, bortezomib and lenalidomide against 6 cell lines derived from hematological malignancies was investigated using trypan blue staining, flow cytometry-based detection of activated caspases, Annexin V assays, immunohistochemistry studies (KI-67 and caspase-3 staining) and the immature-myeloid-information (IMI) technique. Perifosine and bortezomib induced concentration- and time-dependent cytotoxicity in all cell lines tested. Perifosine together with bortezomib largely exerted additive or synergistic effects with combination indices ranging from 1.13 to 0.22 for combined efficacies of 25% to 75% after 24-hour incubation. Lenalidomide-triggered cytotoxicity was low in all cell lines tested with any assay (less than 10% compared to the negative control). Finally, perifosine, but not bortezomib or lenalidomide, significantly increased the number of cells detected in the IMI channel. Perifosine and bortezomib- but not lenalidomide- trigger substantial cytotoxicity by caspase activation and mainly act additively or synergistically. The IMI technique might be a useful tool for studying cytotoxicity of agents like perifosine that interact mainly with the cellular membrane.
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Metadata
Title
In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and lenalidomide against different cell lines
Authors
Martin Schmidt-Hieber
Robert Dabrowski
Andreas Weimann
Babette Aicher
Philipp Lohneis
Antonia Busse
Eckhard Thiel
Igor W. Blau
Publication date
01-04-2012
Publisher
Springer US
Published in
Investigational New Drugs / Issue 2/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-010-9576-2

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