The phosphoinositide 3-kinase/Akt pathway is activated by daunorubicin in human acute myeloid leukemia cell lines.
FEBS Lett
; 452(3): 150-4, 1999 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-10386580
ABSTRACT
Daunorubicin induces apoptosis in myeloid leukemia cells by activation of neutral sphingomyelinase and ceramide generation occurring 4-10 min after daunorubicin addition. We show here that daunorubicin is able to increase the phosphoinositide 3-kinase activity and enhance intracellular phosphoinositide 3-kinase lipid products prior to ceramide generation. Daunorubicin activates Akt, a downstream phosphoinositide 3-kinase effector. Interestingly, the phosphoinositide 3-kinase inhibitors wortmannin and LY294002 accelerate daunorubicin-induced apoptosis in U937 cells. The phosphoinositide 3-kinase/Akt pathway has been involved in cell survival following serum deprivation, tumor necrosis factor alpha, anti-Fas and UV radiations. Our results suggest that anti-tumor agents such as daunorubicin may also activate anti-apoptotic signals that could contribute to drug resistance.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Daunorrubicina
/
Fosfatidilinositol 3-Quinases
Limite:
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article