8-epipuupehedione and Leukemia--Promyelocytic--Acute

We have previously reported that 8-epipuupehedione, a synthetic derivative of sesquiterpenes found in several kinds of sponges, is a potent inhibitor of angiogenesis. Here, we show that 8-epipuupehedione is also a potent anti- leukaemic compound, targeting three hallmarks of malignancy: proliferation, survival and extra-cellular matrix re-modelling. To fulfil this goal, we use the HL-60 promyeolocytic cells as our model system and the following experimental procedures: cell growth assay, Hoetsch staining, cell cycle analysis and DNA fragmentation, caspase 3 activity and zymographic assays. Our results show that this compound inhibits proliferation and has potent and specific pro-apoptotic effects on HL-60 promyelocytic cells, inducing their nuclei and DNA fragmentation, as well as caspase 3 activity activation. Furthermore, 8-epipuupehedione strongly inhibits matrix metalloproteinase-2 and urokinase production by HL-60 cells. These results suggest that 8-epipuupehedione could be an attractive drug for further evaluation in the treatment of leukemia.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Aorta; Apoptosis; Caspase 3; Cattle; Cell Cycle; Cell Proliferation; Cell Survival; Cells, Cultured; DNA Fragmentation; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Vascular; Enzyme Activation; Extracellular Matrix; HL-60 Cells; Humans; Inhibitory Concentration 50; Leukemia, Promyelocytic, Acute; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Terpenes; Time Factors; Urokinase-Type Plasminogen Activator