Apoptosis of murine L1210 leukemia cells induced by 2-acetyl-3-(6-methoxybenzothiazo)-2-ylamino-acrylonitril involves ROS-mitochondrial mediated death signalling and activation of p38 MAPK
Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology STU, Radlinského 9, 812 37 Bratislava
a Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava
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Abstract: Benzothiazoles are multitarget agents with a broad spectrum of biological activity. Some of them are now in cancer clinical testing. 2-acetyl-3-(6-methoxybenzothiazo)- 2-ylaminoacrylonitril (AMBAN) is a new synthetically prepared derivative which showed cytotoxic effects on cancer cells in our previous study. The aim of the present study was to examine the cytotoxic/antiproliferative effect of AMBAN and induction of apoptosis on murine leukemia L1210 cells. Further, the molecular mechanism involved in AMBAN-induced apoptosis was investigated. Benzothiazole acted cytotoxically on leukemia L1210 cells and induced apoptotic cell death. AMBAN elevated the level of ROS in time-dependent manner, decreased the mitochondrial membrane potential, activated caspases 9 and 3, induced the cytochrome c release, PARP (poly (ADP-ribose) polymerase) cleavage and led to intranucleosomal DNA fragmentation. It can be concluded that AMBAN induced apoptosis in L1210 cells through mitochondrial/caspase 9/caspase 3-dependent pathway. p38 MAPK and not JNK or ERK was associated with the proapoptotic activity of AMBAN.
Keywords: benzothiazole derivative, apoptosis, caspase, reactive oxygen species, leukemia, p38 MAPK
Full paper in Portable Document Format: acs_0055.pdf
Acta Chimica Slovaca, Vol. 3, No. 1, 2010, pp. 15—28