Inhibition of PI3-kinase sensitises HL60 human leukaemia cells to both chemotherapeutic drug- and Fas-induced apoptosis by a JNK independent pathway

Inhibition of PI3-kinase sensitises HL60 human ...

Title	Inhibition of PI3-kinase sensitises HL60 human leukaemia cells to both chemotherapeutic drug- and Fas-induced apoptosis by a JNK independent pathway
Author(s)	D. O'Gorman, S. McKenna, A. McGahon, T. Cotter
Journal	Leukemia research
Date	2001
Volume	25
Issue	9
Start page	801
End page	811
Abstract	Increasing resistance to chemotherapeutic regimes remains a serious problem in the treatment of acute myeloid leukaemia. We have shown that phosphatidylinositol (PI) 3-kinase inhibition significantly sensitises the AML derived cell line, HL60 to chemotherapeutic drug- and Fas-induced apoptosis. PI3-kinase inhibition significantly potentiates cytotoxic drug-induced c-jun N-terminal kinase (JNK) activation, reported to be a requirement for apoptosis. However, JNK inhibition does not enhance cell viability following treatment with drug and inhibitor. Furthermore, PI3-kinase inhibition significantly increases sensitivity to apoptosis mediated by an exogenous receptor agonist, again by a JNK independent mechanism. These results suggest that PI3-kinase inhibitors could be of significant therapeutic importance, lowering the threshold for apoptosis induced by both chemotherapy and cell-mediated immune response.
ISSN	0145-2126

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