Inhibition of phosphatidylinositol 3-kinase causes apoptosis in retinoic acid differentiated hl-60 leukemia cells.
Phosphatidylinositol 3-kinase (PI3-K) signaling may inhibit apoptosis in neoplastic cells. The PI-3K inhibitor wortmannin renders cells apoptosis-prone. Inducers of differentiation may also cause apoptosis. To detect the effect of wortmannin on the survival of differentiated human acute promyeloid leukemia cells, HL-60 cells were induced to differentiation with treatment of all trans-retinoic acid (ATRA) followed by treatment with wortmannin. Results showed that apoptosis occurred in cells that underwent differentiation, but not in undifferentiated HL-60 cells. The pro-apoptotic molecule, Bad, played a role in this apoptotic mechanism. Thus, the survival of differentiated HL-60 cells induced by ATRA depends on the ability of the PI3-K pathway to transduce survival signals; the PI3-K inhibitor, wortmannin, can induce apoptosis of differentiated HL-60 cells. These results may indicate a novel method for treating cancer with differentiation induction and signal pathway regulation.
Ma
Jin
J
Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
Liu
Qiang
Q
Zeng
Yi-Xin
YX
D000730:Androstadienes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D053938:DNA Fragmentation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D000077191:Wortmannin; D051025:bcl-Associated Death Protein
D000730:Androstadienes; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014212:Tretinoin; D000077191:Wortmannin; D051025:bcl-Associated Death Protein; C494819:BAD protein, human