Antitumour activity of Annona squamosa seed extracts is through the generation of free radicals and induction of apoptosis

The plant, Annona squamosa traditionally known as custard apple possesses potent bioactive principles in all its parts. The effect of aqueous and organic extracts from defatted seeds of A. squamosa was studied on a rat histiocytic tumour cell line, AK-5. Both the extracts caused significant apoptotic tumour cell death with enhanced caspase-3 activity, down regulation of antiapoptotic genes Bcl-2 and Bcl(XL), and enhanced the generation of intracellular ROS, which correlated well with the decreased levels of intracellular GSH. In addition, DNA fragmentation and annexin-V staining confirmed that the extracts induced apoptosis in tumour cells through the oxidative stress. Aqueous extracts of A. squamosa seeds possessed significant antitumor activity in vivo against AK-5 tumor.