cytochrome-c-t and alpha-methylene-gamma-butyrolactone

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).

Topics: 4-Butyrolactone; Antineoplastic Agents; Apoptosis; Caspases; Cell Division; Cell Survival; Cytochromes c; G2 Phase; HL-60 Cells; Humans; Mitogen-Activated Protein Kinases; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; U937 Cells