Document Detail


In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and lenalidomide against different cell lines.
MedLine Citation:
PMID:  21080211     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Martin Schmidt-Hieber; Robert Dabrowski; Andreas Weimann; Babette Aicher; Philipp Lohneis; Antonia Busse; Eckhard Thiel; Igor W Blau
Publication Detail:
Type:  Journal Article     Date:  2010-11-16
Journal Detail:
Title:  Investigational new drugs     Volume:  30     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  480-9     Citation Subset:  IM    
Affiliation:
Medizinische Klinik III (Hämatologie, Onkologie und Transfusionsmedizin), Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany, martin.schmidt-hieber@charite.de.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A new diaryl urea compound, D181, induces cell cycle arrest in the G1 and M phases by targeting rece...
Next Document:  Production of hyperthermostable GH10 xylanase Xyl10B from Thermotoga maritima in transplastomic plan...