| Affiliation: | 1.Department of Radiation Oncology,David Geffen School of Medicine at UCLA,Le Conte Avenue,USA;2.Department of Urology,University Hospital Münster,Münster,Germany;3.Department of Radiation Oncology,University Hospital Freiburg,Freiburg,Germany |
| Abstract: | Background By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. |
