The anticancer effect of selenium : study of its role in DNA repair activity and resistance to oxidative stress
Selenium was recognized as an important micronutrient for both humans and animals. Several studies showed that increased selenium in the diet might be beneficial against liver, colon, pancreas and prostate cancer. The anticarcinogenic actions of Se occur at the systemic, cellular and nuclear level. These actions may also involve the immune system and thus cannot be interpreted by a single mechanism. Until now its mechanisms of action are not well understood. The objective of this study was to investigate the effect of selenocompounds at low doses on DNA repair capacity in the p53-proficient LNCaP prostate cancer cells. This work is divided into three parts. The first part of the work was devoted to study the effect of two selenocompounds (SS and SM) on the cytotoxic and genotoxic properties of various oxidative and non oxidative stresses. The results showed that low doses of Se pre-treatment stimulates selenoprotein synthesis, protects against toxicity and oxidative DNA damage induced by UVA or H2O2 but not by MMS or UVC. The second part of our investigation was devoted to the influence of selenium supplementation on DNA repair capacity. Our work clearly showed an increase in excision efficiency of the glycosylases activity that was not necessarily correlated with an increase of gene expression and/or protein levels. Finally, the third part of our work was devoted to the optimization of Host Cell Reactivation assay (HCR) to study the DNA repair capacity in cellulo, in order to target the partners involved in the signalling pathway affected by selenium supplementation. In conclusion, we could image that the mechanism of action of selenium is represented by a delicate balance between activation and repression of protein activity that induces conformational changes of several proteins more or less directly involved in DNA repair and progression of cell growth.