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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-04

AUTHORS

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

ABSTRACT

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. More... »

PAGES

480-489

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-010-9576-2

DOI

http://dx.doi.org/10.1007/s10637-010-9576-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002985170

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21080211


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RDF/XML is a standard XML format for linked data.

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