Induction of G2 -M phase arrest and apoptosis by α-methylene-γ-butyrolactones in human leukemia cells

• Published in: Cancer letters Vol. 269; no. 1; pp. 139 - 147
• Main Authors: Torres, Fernando, Quintana, José, Cabrera, Javier, Loro, Juan F, León, Francisco, Bermejo, Jaime, Estévez, Francisco
• Format: Journal Article
• Language: English
• Published: Ireland 28.09.2008
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Caspases - physiology; Cell Division - drug effects; Cell Survival - drug effects; Cytochromes c - metabolism; G2 Phase - drug effects; Hematology, Oncology and Palliative Medicine; HL-60 Cells; Humans; Mitogen-Activated Protein Kinases - physiology; Poly(ADP-ribose) Polymerases - metabolism; Reactive Oxygen Species - metabolism; U937 Cells; α-Methylene-γ-butyrolactones; Reactive oxygen species; PARP cleavage; Caspases; DNA fragmentation; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.04.028

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).