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 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
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 37 Issue 5-6 Pg. 605-12 (May 2010) ISSN: 1440-1681 [Electronic] Australia
• PMID: 20082627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Dioxolanes
• Reactive Oxygen Species
• pipoxolan
• Caspase 3

Topics

• 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
• G1 Phase (drug effects)
• HL-60 Cells
• Humans
• Leukocytes, Mononuclear (drug effects, metabolism, pathology)
• Molecular Structure
• Reactive Oxygen Species (metabolism)
• Resting Phase, Cell Cycle (drug effects)