Epoxyazadiradione Purified from the Azadirachta indica Seed Induced Mitochondrial Apoptosis and Inhibition of NFB Nuclear Translocation in Human Cervical Cancer Cells

Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta indica) plant. In the present study, we have purified EAD from Neem seed and studied its anticancer potential in human cervical cancer (HeLa) cells. Cell proliferation inhibition studies indicated that the GI(50) value of EAD is 7.5 +/- 0.0092M in HeLa cells, whereas up to 50M concentrations EAD did not affect the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth of both HeLa and H9C2 cells with a GI(50) value of 2.92 +/- 1.192 and 4.22 +/- 1.568M, respectively. Nuclear DNA fragmentation, cell membrane blebbing, phosphatidylserine translocation, upregulation of Bax, caspase 3 activity and poly (ADP ribose) polymerase cleavage and downregulation of BCl2 in HeLa cells on treatment with EAD indicated the apoptotic cell death. Increase in caspase 9 activity and release of active cytochrome c to the cytoplasm on treatment with EAD confirmed that the apoptosis was mediated through the mitochondrial pathway. Epoxyazadiradione also inhibited the nuclear translocation of nuclear factor B in HeLa cells. Thus, our studies demonstrated EAD as a potent and safe chemotherapeutic agent when compared with the standard drug cisplatin that is toxic to both cancer and normal cells equally. Copyright (c) 2017 John Wiley & Sons, Ltd.