ABSTRACT
The effect of mitokorrectine (complex native oligopeptides isolated from neonatal pig brain) on endothelial cells in culture was investigated. It was revealed that the drug concentration-dependently induces angiogenesis in vitro. Mitogen effect of Mitokorrectine was shown by MTT-test and routine cell count in concentration diapason (0.1-1 mg/ml) which means an increased number of cells by 25 +/- 5% and cell subpopulation of proliferative pool (G2/M+S) 1,8 times in concentration diapason mitokorrectine (0.01-0.05 mg/ml) in comparison with control. In 3-D culture and in stationary phase we detected induction of differentiation of endothelial cells, a decrease the level of NO production and enhancement of glucose metabolism and stimulation of formation of capillary-like tubes.
Subject(s)
Cell Proliferation/drug effects , Endothelial Cells/drug effects , Neovascularization, Physiologic/drug effects , Oligopeptides/pharmacology , Animals , Animals, Newborn , Brain Chemistry , Cell Cycle/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Endothelial Cells/metabolism , Flow Cytometry , Glucose/metabolism , Liver/chemistry , Mitochondria/chemistry , Nitric Oxide/metabolism , Pancreas/chemistry , SwineABSTRACT
Connection between the level of NO generation and its cytotoxic influence was investigated on two models of tumor cells (breast adenocarcinoma MCF-7) culture: monolayer and spheroids. Conditions of microenvironment were modified by Ca2+ channels blockers: EGTA, nitrendipine and Cl-lanthan. It was discovered in the work that deviation in concentration of extracellular Ca2+ under the influence of EGTA leads to reducing of the level of extracellular NO to 50% (P < or = 0.05) of control and increasing of the number of live cells by 10-40% (P < or = 0.05). Nitrendipin has the properties selective Ca2+ channels blocker that reduced the level of NO by 35-70% (P < or = 0.05), depending on the substances concentration and time of incubation. At that time proliferation potential of cells increased by 10-35% (P < or = 0.05). NO production in MCF-7 cells under the influence of Cl-lanthan in concentration of 0.01 and 0.1 mM is reduced by 50-60%, as compared with the control. But it had no influence on the number of live cells. On 2-D and 3-D models of tumor growth it was demonstrated that extracellular NO production in monolayer of MCF-7 was 3.2 pmol for 10(6) cells and for spheroids it was 8.5 pmol.
