| 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...