The anti-angiogenic 8-epipuupehedione behaves as a potential anti-leukaemic compound against HL-60 cells.
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.
Martínez-Poveda
Beatriz
B
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga, Spain.
Quesada
Ana R
AR
Medina
Miguel Angel
MA
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
C481243:8-epipuupehedione; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D013729:Terpenes; D014568:Urokinase-Type Plasminogen Activator; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2