Document Detail

PI3K Inhibitor D-116883 is Effective in In Vitro Models of Ovarian Cancer.
MedLine Citation:
PMID:  22593485     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: D-116883 (Aeterna Zentaris GmbH, Frankfurt, Germany) is an orally effective drug that acts via inhibition of phosphatidylinositol 3-kinase (PI3K). The PI3K/AKT signal transduction pathway is involved in ovarian cancer tumorigenesis. Phosphatase and Tensin homolog (PTEN) loss and other activating mutations frequently contribute to the activation of this pathway. We tested whether D-116883 exerts cytostatic effects in in vitro models of ovarian cancer and analyzed the induced programmed cell death.
MATERIALS AND METHODS: We evaluated the potency of D-116883 in four ovarian carcinoma cell lines with different cellular assays. The effects of D-116883 on cell proliferation was analysed by crystal-violet staining and tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay. The capacity for anchorage-independent growth was analyzed in two ovarian carcinoma cell lines without and with D-116883 addition by using the soft agar assay. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed. Cells were incubated with multicaspase inhibitor benzyloxycarbonyl-val-ala-asp(OMe)-fluoromethylketone (zVAD) and inhibitor of necroptosis necrostatin.
RESULTS: Growth inhibition occurred in all ovarian carcinoma cell lines studied (A2780, A2780cis, OAW42 and SKOV3) in a micromolar range (IC(50)<1 μM). By using soft agar assay, a reduced capacity for anchorage-independent growth, a hallmark of tumor cells, caused by D-116883 was demonstrated. Cell cycle analyses showed that D-116883 dose-dependently increased apoptotic cells. Multicaspase inhibitor zVAD and inhibitor of necroptosis necrostatin did not abrogate the growth-inhibiting effect of the compound.
CONCLUSION: PI3K inhibitor D-116883 showed substantial cytotoxic effects in various in vitro models of ovarian cancer. Our results make D-116883 a good candidate for further ovarian cancer research including in vivo experiments.
A Honig; J C Hahne; S Meyer; P Kranke; S Häusler; J Diessner; J Dietl; J B Engel
Related Documents :
2699855 - Positional information revisited.
20152795 - Cell biology meets biophysics to unveil the different mechanisms of penetratin internal...
11544035 - Intercellular junctions and cellular polarity: the par-apkc complex, a conserved core c...
20445765 - Polymer microlenses for quantifying cell sheet mechanics.
6229065 - The function of thymic reticuloepithelial cells in new zealand mice.
22766505 - Pi3k/akt and erk regulate retinoic acid-induced neuroblastoma cellular differentiation.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2035-41     Citation Subset:  IM    
Department of Gynecology and Obstetrics, Medical University of Würzburg, Josef Schneider Str. 4, 97080 Würzburg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Similar Incidences of TP53 Deletions in Extramedullary Organ Infiltrations, Soft Tissue and Osteolys...
Next Document:  Scattering effects of irradiation on surroundings calculated for a small dental implant.