Document Detail


Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase.
MedLine Citation:
PMID:  20082627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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-Hsi Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-17
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  37     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-06-09     Completed Date:  2010-10-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  605-12     Citation Subset:  IM    
Affiliation:
School of Pharmacy, China Medical University, 91, Hsueh-Shih Rd., Taichung, 404, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  pharmacology*
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / metabolism
Cell Culture Techniques
Cell Proliferation / drug effects*
Cell Survival / drug effects
DNA Fragmentation / drug effects
Dioxolanes / chemistry,  pharmacology*
Flow Cytometry
G0 Phase / drug effects*
G1 Phase / drug effects*
HL-60 Cells
Humans
Leukocytes, Mononuclear / drug effects,  metabolism,  pathology
Molecular Structure
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dioxolanes; 0/Reactive Oxygen Species; 23744-24-3/pipoxolan; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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