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 G0/G1 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).
| Original language | English |
|---|---|
| Pages (from-to) | 605-612 |
| Number of pages | 8 |
| Journal | Clinical and Experimental Pharmacology and Physiology |
| Volume | 37 |
| Issue number | 5-6 |
| DOIs | |
| Publication status | Published - 2010 |
| Externally published | Yes |
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Keywords
- Anti-proliferation
- Apoptosis
- Caspase 3
- Pipoxolan
- Reactive oxygen species
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Pharmacology
- Medicine(all)
Cite this
Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase. / Sheu, Ming Jyh; Chou, Pei Yu; Huang, Chin Shiu; Tsai, I. Chun; Chien, Yi Chung; Lin, Sung Yuan; Tsai, Huei Yann; Cheng, Hsu Chen; Wu, Chieh His.
In: Clinical and Experimental Pharmacology and Physiology, Vol. 37, No. 5-6, 2010, p. 605-612.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase
AU - Sheu, Ming Jyh
AU - Chou, Pei Yu
AU - Huang, Chin Shiu
AU - Tsai, I. Chun
AU - Chien, Yi Chung
AU - Lin, Sung Yuan
AU - Tsai, Huei Yann
AU - Cheng, Hsu Chen
AU - Wu, Chieh His
PY - 2010
Y1 - 2010
N2 - 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 G0/G1 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).
AB - 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 G0/G1 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).
KW - Anti-proliferation
KW - Apoptosis
KW - Caspase 3
KW - Pipoxolan
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=77951121047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951121047&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1681.2010.05358.x
DO - 10.1111/j.1440-1681.2010.05358.x
M3 - Article
C2 - 20082627
AN - SCOPUS:77951121047
VL - 37
SP - 605
EP - 612
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
SN - 0305-1870
IS - 5-6
ER -