Peer-Reviewed Journal Details
Mandatory Fields
O'Gorman, DM,McKenna, SL,McGahon, AJ,Cotter, TG;
2001
January
Official Journal of The Leukemia Society of America
Inhibition of PI3-kinase sensitises HL60 human leukaemia cells to both chemotherapeutic drug- and Fas-induced apoptosis by a JNK independent pathway
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Optional Fields
AML apoptosis PI3-kinase chemotherapeutic drugs Fas JNK NF-KAPPA-B APO-1/FAS RECEPTOR/LIGAND SYSTEM MEDIATED APOPTOSIS ACTIVATION KINASE CD95 DEATH RAS SURVIVAL CANCER
25
801
811
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. P13-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, P13-kinase inhibition significantly increases sensitivity to apoptosis mediated by an exogenous receptor agonist, again by a JNK independent mechanism. These results suggest that P13-kinase inhibitors could be of significant therapeutic importance, lowering the threshold for apoptosis induced by both chemotherapy and cell-mediated immune response. (C) 2001 Elsevier Science Ltd. All rights reserved.
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