Apoptosis induced by 2-acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile in human leukemia cells involves ROS-mitochondrial mediated death signaling and activation of p38 MAPK.
Benzothiazoles are multitarget agents with broad spectrum of biological activity. 2-Acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile (AMBAN) is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects towards tumor cells. The aim of the present study was to examine the antiproliferative and apoptosis inducing activities of AMBAN towards human leukemia HL60 and U937 cells. Further, the molecular mechanism involved in AMBAN-induced apoptosis was investigated. Benzothiazole inhibited the growth and induced programmed cell death of HL60 and U937 cells. In addition, AMBAN elevated the level of reactive oxygen species, decreased the mitochondrial membrane potential, activated caspases 9 and 3, induced the cytochrome c release and PARP cleavage and led to intranucleosomal DNA fragmentation. Further, p38 MAPK was associated with the apoptotic activity of AMBAN. It can be concluded that AMBAN-induced apoptosis in HL60 and U937 cells through mitochondrial/caspase 9/caspase 3-dependent pathway.
Repicky
A
A
Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, Bratislava, Slovakia. andrej.repicky@stuba.sk
Jantova
S
S
Cipak
L
L
D000181:Acrylonitrile / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles / Q000494:pharmacology*; D020169:Caspases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
C539700:2-acetyl-3-(6-methoxybenzothiazo)-2-ylaminoacylonitrile; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D000181:Acrylonitrile