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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 and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2010 May; Vol. 37 (5-6), pp. 605-12. Date of Electronic Publication: 2010 Jan 17. - 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 microg/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(0)/G(1) 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).
- Subjects :
- Antineoplastic Agents chemistry
Blotting, Western
Caspase 3 metabolism
Cell Culture Techniques
Cell Survival drug effects
DNA Fragmentation drug effects
Dioxolanes chemistry
Flow Cytometry
HL-60 Cells
Humans
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear pathology
Molecular Structure
Reactive Oxygen Species metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Proliferation drug effects
Dioxolanes pharmacology
G1 Phase drug effects
Resting Phase, Cell Cycle drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1681
- Volume :
- 37
- Issue :
- 5-6
- Database :
- MEDLINE
- Journal :
- Clinical and experimental pharmacology & physiology
- Publication Type :
- Academic Journal
- Accession number :
- 20082627
- Full Text :
- https://doi.org/10.1111/j.1440-1681.2010.05358.x