Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/68523
標題: Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G(0)/G(1) phase
作者: Sheu, M.J.
Chou, P.Y.
Huang, C.S.
Tsai, I.C.
Chien, Y.C.
Lin, S.Y.
Tsai, H.Y.
Cheng, H.C.
Wu, C.H.
關鍵字: anti-proliferation
apoptosis
caspase 3
pipoxolan
reactive oxygen
species
oxidative stress
dna damage
apoptosis
death
activation
target
identification
stimulation
mechanisms
pathways
期刊/報告no:: Clinical and Experimental Pharmacology and Physiology, Volume 37, Issue 5-6, Page(s) 605-612.
摘要: P>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 mu g/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).
URI: http://hdl.handle.net/11455/68523
ISSN: 0305-1870
文章連結: http://dx.doi.org/10.1111/j.1440-1681.2010.05358.x
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