INTRODUCTION: Statins have benefits independent of the plasma @entity165 properties among @entity5 @entity1 and tissue factor (TF)/FVIIa induce PI3-kinase/ @entity584 dependent anti-apoptosis during serum starvation. We analyzed how @entity3413 induces apoptosis in @entity1 @entity0 cells and the influence of FVIIa and/or @entity6236 on the proposed apoptosis. MATERIALS AND METHODS: MDA-MB-231 cells were serum starved or treated with 5 microM @entity3413 and incubated with 10 and 100 nM FVIIa or 5/130 nM FVIIa/FX. @entity3547 was analyzed by confocal microscopy and @entity522 , nuclear fragmentation, and NFkappaB translocation were measured using the ArrayScan microscope. mRNA for @entity588 , @entity584 and TF were analyzed with RT-PCR or TaqMan. Protein levels and phosphorylation of PKB/ @entity584 were determined by western blotting. RESULTS AND CONCLUSIONS: @entity3413 -induced apoptosis was recorded at 48 h in the MDA-MB-231 cells. Addition of FVIIa to the cells induced PKB/ @entity584 phosphorylation at 24 h and rescued serum-deprived cells from apoptosis. However, in the presence of @entity3413 we were unable to report any phosphorylation of PKB/ @entity584 or anti-apoptotic effect mediated by the TF/FVIIa or TF/FVIIa/ @entity6236 complexes. This was due to a @entity3547 -dependent retention of NFkappaB to the cytosol at 12 h which led to a transcriptional down-regulation of the anti-apoptotic protein @entity588 as well as reduced @entity584 mRNA production at 24 h and thus diminished levels of @entity584 protein. A transcriptional down-regulation of TF at 12 h possibly also contributed to the absent anti-apoptotic signaling. These results thereby support a role for @entity3413 in @entity5 treatment and emphasize the importance of @entity584 in TF-signaling.

XXXX induces apoptosis in @entity1 @entity0 cells in a NFkappaB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/ @entity6236 .

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity522 :: ('836', 'Gene') :: ['caspase-3'] @entity3413 :: ('MESH:D019821', 'Chemical') :: ['Simvastatin', 'simvastatin'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity588 :: ('596', 'Gene') :: ['BCL-2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity3547 :: ('387', 'Gene') :: ['RhoA'] @entity584 :: ('207', 'Gene') :: ['AKT1', 'AKT', 'PKB/AKT'] @entity6236 :: ('2159', 'Gene') :: ['FXa'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity3413 :: (MESH:D019821,Chemical) :: ['Simvastatin']
