Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase–Akt/PKB survival pathway
作者:
Gerald Ruiter,
Shuraila Zerp,
Harry Bartelink,
Wim van Blitterswijk,
Marcel Verheij,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 2
页码: 167-173
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: alkyl-lysophospholipids;apoptosis;Akt/PKB;phosphatidylinositol 3-kinase;SAPK/JNK
数据来源: OVID
摘要:
Synthetic alkyl-lysophospholipids (ALPs) represent a new class of anti-tumor agents that target cell membranes and induce apoptosis. However, the exact mechanisms by which ALPs exert these effects remain unclear. Here, we investigated in the epithelial carcinoma cell lines A431 and HeLa the effect of three clinically relevant ALPs [Et-18-OCH3(Edelfosine), HePC (Miltefosine) and D-21266 (Perifosine)] on the phosphatidylinositol 3-kinase (PI3K)–Akt/PKB survival pathway. We found that growth factor-induced Akt/PKB activation in these cells is dependent on PI3K and that all three ALPs inhibited this pathway in a dose-dependent manner. We further showed that inhibition of the PI3K–Akt/PKB pathway by wortmannin or ALPs is associated with activation of the pro-apoptotic SAPK/JNK pathway. Inhibition of the PI3K–Akt/PKB survival pathway represents a novel mode of action of ALPs that may significantly contribute to the induction of apoptosis.
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