Oleandrin induces apoptosis in human, but not in murine cells: dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity.
Mol Immunol
; 44(9): 2292-302, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17173971
ABSTRACT
Common practice to evaluate the efficacy of any compound as drug is done in cell-based in vitro system followed by in vivo murine model prior to clinical trial in human. Cardiac glycosides are very effective to kill human cells, but not murine cells. In this report, we describe the comparative molecular mechanism of oleandrin, a cardiac glycoside action in human and murine cells. Treatment with oleandrin facilitated nuclear translocation of FKHR in human, but not murine cells by dephosphorylating Akt. It activated MAPK and JNK in human, but not in murine cells and also induced expression of FasL leads to apoptosis in human cells as detected by assaying caspases activation, PARP cleavage, nuclear fragmentation, and annexin staining. Oleandrin interacted with human plasma membrane as evaluated by HPLC, altered its fluidity as detected by DPH binding, inhibited Na+/K+-ATPase activity, and increased intracellular free Ca2+ level followed by calcineurin activity only in human, but not in murine cells. Results suggest that human plasma membrane might be different than murine, which interact with oleandrin that disturb Na+/K+-ATPase pump resulting in the calcification followed by induction of Ca2+-dependent cellular responses such as apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardenolídeos
/
Apoptose
/
Proteínas Proto-Oncogênicas c-akt
/
Proteína Ligante Fas
/
Fluidez de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Índia