The effects of oxidative stress on collagen and DNA biosynthesis, beta-galactosidase activity, the expression of the beta-integrin receptor, FAK, the insulin-like growth factor-I receptor (IGF-IR), the hypoxia-inducible factor-1 (HIF-1), and the mitogen-activated protein kinases (MAP/ERK(1), ERK(2)) were evaluated in human endometrial carcinoma cells. Subconfluent cells were subjected to oxidative stress with 30 microM t-butylhydroperoxide (t-BHP) for 1 h per day over the course of 5 days. It was found that oxidative stress contributed to an increase in the beta-galactosidase activity as well as to the inhibition of collagen and DNA biosynthesis. The mechanism of the process was found at the level of IGF-IR and HIF-1 alpha. An increase in the expression of HIF-1 alpha and a decrease in the expression of IGF-IR were observed in the cells subjected to oxidative stress. The role of IGF-IR signalling in the process was confirmed by an experiment showing downregulation of MAP kinases ERK(1) and ERK(2) expression in the studied cells. This phenomenon is probably responsible for the drastic inhibition of protein (up to 40 % of control) and DNA biosynthesis (up to 65 % of control) in the cells. An addition of tiliroside to the cells medium restored all parameters to the control level, including IGF-IR and HIF-1 alpha expressions. The data suggest that the antioxidative activity of tiliroside isolated from Potentilla argentea may originate at the level of IGF-IR and HIF-1 alpha signalling.
Georg Thieme Verlag KG Stuttgart.New York.