Open AccessThe anti‐angiogenic 8‐epipuupehedione behaves as a potential anti‐leukaemic compound against HL‐60 cells
Author(s) -
MartínezPoveda Beatriz,
Quesada Ana R.,
Medina Miguel Ángel
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00134.x
Subject(s) - dna fragmentation , apoptosis , cell growth , angiogenesis , chemistry , cancer research , matrix metalloproteinase , acute promyelocytic leukemia , microbiology and biotechnology , leukemia , cell culture , biology , biochemistry , programmed cell death , immunology , genetics , retinoic acid
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.