Do altered activities of superoxide dismutases and the level of Nf-κB modulate the effects of gamma radiation in HeLaS3 cells?

摘要

Most experimental models, including cell culture studies, have demonstrated that over-expression of manganese superoxide dismutase (MnSOD) in cells bearing a carcinoma phenotype has anti-proliferative and tumour suppression characteristics. In contrast, when cervical carcinoma biopsies express MnSOD, there is a poor prognosis and resistance to radiation therapy. The results herein indicate that human cervical adenocarcinoma (HeLaS3) cells have increased MnSOD activity (up to 50 % of the total SOD activity) due to low expression of its repressor p53 and a high level of oxidative stress arising from the cell culture conditions. High MnSOD activity may be related to HeLaS3 cell radioresistance, illustrated by a high IC50 of 3.4 Gy and by a relatively high level of cell viability after gamma irradiation. In contrast to MnSOD activity, cytosolic CuZnSOD activity decreased after ionising radiation. The catalase (Cat) activity was unchanged. IR also increased the nitric oxide synthase (NOS) activity. Such conditions lead to increased concentrations of the superoxide radical, hydrogen peroxide and NO·, which together may be responsible for the decreased expression of NF-κB and unaltered Cat activity. Therefore, the disturbed redox balance within HeLaS3 cells may be responsible for the cytotoxicity observed at higher irradiation doses. It could be concluded that inhibition of the CuZnSOD activity may be an important target for the selective killing of radioresistant cancer cells.