Induction of G2-M phase arrest and apoptosis by alpha-methylene-gamma-butyrolactones in human leukemia cells.

Authors:
Fernando Torres
Fernando Torres
University of Texas Southwestern Medical Center
United States
Jose Quintana
Jose Quintana
Hospital Galdakao-Usansolo (Osakidetza)-Red de Investigación en Servicios de Salud en Enfermedades Crónicas
Spain
Javier Cabrera
Javier Cabrera
Facultad de Ciencias Ambientales y Bioquímica
Juan F Loro
Juan F Loro
Departamento de Ciencias Clínicas
Francisco Leon
Francisco Leon
National Institutes of Health
United States
Jaime Bermejo
Jaime Bermejo
Università di Ferrara
Italy
Francisco Estevez
Francisco Estevez
Juan Canalejo Hospital
Spain

Cancer Lett 2008 Sep 2;269(1):139-47. Epub 2008 Jun 2.

Department of Biochemistry, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.

In this study, we investigated the effect of three synthetic alpha-methylene-gamma-butyrolactones (MBL) on viability of 10 human tumor cell lines and found that these lactones were highly cytotoxic against leukemia cells. Studies performed on HL-60 cells indicate that MBL induce G(2)-M arrest and apoptosis through a caspase-dependent mechanism. Apoptosis was associated to cytochrome c release, cleavage of procaspases-9 and -3, and hydrolysis of PARP. Intracellular reactive oxygen species (ROS) seem to play a key role since high levels of ROS were produced early (<15 min) and apoptosis was completely abrogated by the free radical scavenger N-acetyl-L-cysteine (NAC).

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http://dx.doi.org/10.1016/j.canlet.2008.04.028DOI Listing

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September 2008
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