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Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase.
- Source :
- Clinical & Experimental Pharmacology & Physiology; May/Jun2010, Vol. 37 Issue 5/6, p605-612, 8p, 2 Diagrams, 6 Graphs
- Publication Year :
- 2010
-
Abstract
- 1. The aim of the present study was to investigate the molecular mechanisms by which pipoxolan exerts its inhibitory effects and apoptotic activity in human leukaemia HL-60 cells. 2. The effects of pipoxolan on the proliferation of HL-60 cells and on the distribution of cells within different phases of the cell cycle were investigated indirectly using a Trypan blue assay and a flow cytometer, respectively. The effects of pipoxolan on the apoptosis of HL-60 cells was investigated using DNA fragmentation and flow cytometer. The expression of factors affecting the cell cycle and apoptosis, including p53, p21, Bax, Bcl2, cytochrome c, caspase 3 and caspase 9, was examined by western blotting. 3. At 6.25 μg/mL, pipoxolan significantly induced apoptosis in human leukaemia HL-60 cells after 24 h exposure. In addition, HL-60 cells were arrested in the G<subscript>0</subscript>/G<subscript>1</subscript> phase via the induction of p53/p21 by pipoxolan. Apoptosis was associated with an increased Bax/Bcl-2 ratio, cytochrome c release, cleavage of procaspases-9 and -3 and hydrolysis of poly(ADP-ribose) polymerase. Intracellular reactive oxygen species (ROS) seem to play a key role in the pipoxolan-induced apoptosis, because high levels of ROS were produced early in the drug treatment. Apoptosis was significantly abrogated by the free radical scavenger N-acetylcysteine (NAC). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 37
- Issue :
- 5/6
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 49159649
- Full Text :
- https://doi.org/10.1111/j.1440-1681.2010.05358.x