Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase

Ming Jyh Sheu, Pei Yu Chou, Chin Shiu Huang, I. Chun Tsai, Yi Chung Chien, Sung Yuan Lin, Huei Yann Tsai, Hsu Chen Cheng, Chieh His Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish
Pages (from-to)605-612
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume37
Issue number5-6
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Cell Cycle Resting Phase
G1 Phase
HL-60 Cells
Cell Cycle
Leukemia
Apoptosis
Neoplasms
Caspase 9
Caspase 3
Reactive Oxygen Species
Free Radical Scavengers
Trypan Blue
Poly(ADP-ribose) Polymerases
Acetylcysteine
DNA Fragmentation
Cytochromes c
Human Activities
pipoxolan
Hydrolysis
Western Blotting

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 journalArticle

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. / Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase. In: Clinical and Experimental Pharmacology and Physiology. 2010 ; Vol. 37, No. 5-6. pp. 605-612.
@article{89b90c6c5fe9406b8b757e0f4cd7c085,
title = "Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase",
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).",
keywords = "Anti-proliferation, Apoptosis, Caspase 3, Pipoxolan, Reactive oxygen species",
author = "Sheu, {Ming Jyh} and Chou, {Pei Yu} and Huang, {Chin Shiu} and Tsai, {I. Chun} and Chien, {Yi Chung} and Lin, {Sung Yuan} and Tsai, {Huei Yann} and Cheng, {Hsu Chen} and Wu, {Chieh His}",
year = "2010",
doi = "10.1111/j.1440-1681.2010.05358.x",
language = "English",
volume = "37",
pages = "605--612",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "5-6",

}

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 -