UV irradiation can cause DNA damage, which leads to either cell cycle arrest or apoptosis. As a major transcriptional target of p53 protein in... Show moreUV irradiation can cause DNA damage, which leads to either cell cycle arrest or apoptosis. As a major transcriptional target of p53 protein in response to DNA damage, p21 protein plays critical roles in both cell cycle arrest and apoptosis. However, the specific range of UV doses and functions of p21 protein leading to the determination of cell fate in human androgen-independent prostate cancer cells has not been completely elucidated. Here, we show that low doses of UV irradiation (< 40 J/m2) induced cell cycle arrest with up-regulation of p21 protein. However, high doses of UV irradiation (> 60 J/m2) can induce apoptotic cell death as indicated by caspase-3 activation, which is also consistent with apoptotic morphological changes. Interestingly, p21 protein is degraded at early time course of high-dose UV irradiation-induced apoptosis, pretreatment of proteasome inhibitor MG132 which can block p21 degradation but partially inhibits apoptotic cell death. Consistently, similar results were obtained in both 104-R1 cells and 104-IS cells. Taken together, the results suggest that there is a narrow window of UV doses range that serves as a “switch” point, in which cells make a decision: either cell cycle arrest or cell death. p21 protein serves as a good indicator for both cell cycle arrest and apoptotic cell death post-UV irradiation in human androgen-independent prostate cancer cells. Therefore, p21 may be a potential therapeutic target in prostate cancer. M.S. in Biology, May 2011 Show less
