alexa Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt PKB survival pathway.
Geology & Earth Science

Geology & Earth Science

Journal of Oceanography and Marine Research

Author(s): Ruiter GA, Zerp SF, Bartelink H, van Blitterswijk WJ, Verheij M

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Abstract 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. Copyright 2003 Lippincott Williams & Wilkins This article was published in Anticancer Drugs and referenced in Journal of Oceanography and Marine Research

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