Induction of G2-M phase arrest and apoptosis by alpha-methylene-gamma-butyrolactones in human leukemia cells.
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).
Department of Biochemistry, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
Fernando
F
Torres
José
J
Quintana
Javier
J
Cabrera
Juan F
JF
Loro
Francisco
F
León
Jaime
J
Bermejo
Francisco
F
Estévez
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C014096:alpha-methylene gamma-butyrolactone; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D015107:4-Butyrolactone