| Pipoxolan inhibits proliferation of HL-60 human leukaemia cancer cells by arresting the cell cycle at the G0/G1 phase. | |
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MedLine Citation:
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PMID: 20082627 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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). |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-17 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 37 ISSN: 1440-1681 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-06-09 Completed Date: 2010-10-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 605-12 Citation Subset: IM |
Affiliation:
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School of Pharmacy, China Medical University, 91, Hsueh-Shih Rd., Taichung, 404, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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:
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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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