Caspase-independent cell death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells

Yoshida K, Kubo Y, Kusunoki Y, Morishita Y, Nagamura H, Hayashi I, Kyoizumi S, Seyama T, Nakachi K, Hayashi T
Cell Immunol 255(1-2):61-8, 2009

Summary

To improve our understanding of ionizing radiation effects on immune cells, we investigated steps leading to radiation-induced cell death in MOLT-4, a thymus-derived human leukemia cell. After exposure of MOLT-4 cells to 4 Gy of X-rays, irradiated cells sequentially showed increase in intracellular reactive oxygen species (ROS), decrease in mitochondrial membrane potential, and eventually apoptotic cell death. In the presence of the caspase inhibitor z-VAD-fmk, irradiated cells exhibited necrotic characteristics such as mitochondrial swelling instead of apoptosis. ROS generation was not detected during this necrotic cell death process. These results indicate that radiation-induced apoptosis in MOLT-4 cells requires elevation of intracellular ROS as well as activation of a series of caspases, whereas the cryptic necrosis program–which is independent of intracellular ROS generation and caspase activation–is activated when the apoptosis pathway is blocked. Reproduced from Cellular Immunology 2009;255(1-2):61-8, with permission from © 2008 Elsevier Inc.