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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Plo I,Bettaïeb A,Payrastre B,Mansat-De Mas V,Bordier C,Rousse A,Kowalski-Chauvel A,Laurent G,Lautier Ddoi
10.1016/s0014-5793(99)00631-6keywords:
subject
Has Abstractpub_date
1999-06-11 00:00:00pages
150-4issue
3eissn
0014-5793issn
1873-3468pii
S0014-5793(99)00631-6journal_volume
452pub_type
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