Induction of G(2)-M phase arrest and apoptosis by alpha-methylene-gamma-butyrolactones in human leukemia cells

Abstract

In this study, we investigated the effect of three synthetic α-methylene-γ-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 G2-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).