The anti-angiogenic 8-epipuupehedione behaves as a potential anti-leukaemic compound against HL-60 cells.

Abstract

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.

• Authors: Beatriz Martínez-Poveda, Ana R Quesada, Miguel Angel Medina
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 12 Issue 2 Pg. 701-6 (Apr 2008) ISSN: 1582-1838 [Print] England
• PMID: 18419606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 8-epipuupehedione
• Angiogenesis Inhibitors
• Antineoplastic Agents
• Matrix Metalloproteinase Inhibitors
• Terpenes
• Urokinase-Type Plasminogen Activator
• Caspase 3
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Aorta (cytology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cattle
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects)
• Endothelium, Vascular (cytology)
• Enzyme Activation (drug effects)
• Extracellular Matrix (drug effects)
• HL-60 Cells
• Humans
• Inhibitory Concentration 50
• Leukemia, Promyelocytic, Acute (drug therapy)
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase Inhibitors
• Terpenes (pharmacology)
• Time Factors
• Urokinase-Type Plasminogen Activator (antagonists & inhibitors)