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

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 AMBANinduced 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.