scholarly journals Emetine enhances the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of pancreatic cancer cells by downregulation of myeloid cell leukemia sequence-1 protein

2013 ◽  
Vol 31 (1) ◽  
pp. 456-462 ◽  
Author(s):  
YUJEONG HAN ◽  
SOJUNG PARK ◽  
ANN W. KINYUA ◽  
LADISLAV ANDERA ◽  
KI WOO KIM ◽  
...  
2013 ◽  
Vol 5 (6) ◽  
pp. 1760-1764 ◽  
Author(s):  
WUYUAN ZHOU ◽  
JUN SHI ◽  
ZUOXING NIU ◽  
HONGMIN LUO ◽  
HE TIAN ◽  
...  

Pancreas ◽  
2000 ◽  
Vol 21 (4) ◽  
pp. 392-398 ◽  
Author(s):  
Fumiaki Nozawa ◽  
Masahiko Hirota ◽  
Akihiro Okabe ◽  
Muneyuki Shibata ◽  
Takeshi Iwamura ◽  
...  

2004 ◽  
Vol 15 (7) ◽  
pp. 3266-3284 ◽  
Author(s):  
Romaine Ingrid Fernando ◽  
Jay Wimalasena

Estrogens such as 17-β estradiol (E2) play a critical role in sporadic breast cancer progression and decrease apoptosis in breast cancer cells. Our studies using estrogen receptor-positive MCF7 cells show that E2 abrogates apoptosis possibly through phosphorylation/inactivation of the proapoptotic protein BAD, which was rapidly phosphorylated at S112 and S136. Inhibition of BAD protein expression with specific antisense oligonucleotides reduced the effectiveness of tumor necrosis factor-α, H2O2, and serum starvation in causing apoptosis. Furthermore, the ability of E2 to prevent tumor necrosis factor-α-induced apoptosis was blocked by overexpression of the BAD S112A/S136A mutant but not the wild-type BAD. BAD S112A/S136A, which lacks phosphorylation sites for p90RSK1 and Akt, was not phosphorylated in response to E2 in vitro. E2 treatment rapidly activated phosphatidylinositol 3-kinase (PI-3K)/Akt and p90RSK1 to an extent similar to insulin-like growth factor-1 treatment. In agreement with p90RSK1 activation, E2 also rapidly activated extracellular signal-regulated kinase, and this activity was down-regulated by chemical and biological inhibition of PI-3K suggestive of cross talk between signaling pathways responding to E2. Dominant negative Ras blocked E2-induced BAD phosphorylation and the Raf-activator RasV12T35S induced BAD phosphorylation as well as enhanced E2-induced phosphorylation at S112. Chemical inhibition of PI-3K and mitogen-activated protein kinase kinase 1 inhibited E2-induced BAD phosphorylation at S112 and S136 and expression of dominant negative Ras-induced apoptosis in proliferating cells. Together, these data demonstrate a new nongenomic mechanism by which E2 prevents apoptosis.


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