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
The novel anticancer drug amitosine representing the mixture of thiophosphamide-modified alkaloids from Chelidonium majus L. has been reported to inhibit growth of various solid tumors in vivo. However, its antileukemic activity as well as the mechanisms of anticancer action have not been yet extensively examined. In this study, amitosine treatment at a dose of 100-250 microg/mL for 24 h resulted in dose-dependent inhibition of MT-4 cell proliferation in vitro with apoptosis induction in the setting of the significant G2/M phase arrest (up to 70% of cells). While amitosine induced caspase-3 activation in MT-4 cells, the increase in the number of cells containing the active caspase-3 did not correlate with the increase of apoptotic cell percentage. Western blotting data revealed the accumulation of cytochrome c in cytosolic fraction of MT-4 cells within 6 h after treatment with 100 microg/mL amitosine. To sum up, amitosine has been shown to possess strong antiproliferative and apoptosis-inducing activities in MT-4 cells in vitro, which seem to be mediated partially through caspase-dependent mitochondrial death pathways.
Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cell Cycle/drug effects , Chelidonium/chemistry , Alkaloids/chemistry , Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Division/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , G2 Phase/drug effects , Humans , Precursor Cell Lymphoblastic Leukemia-LymphomaABSTRACT
It is found that 3 months after removal of thyroid gland in rats, a suppression of thymic endocrine function, loss of weight and cellularity occurs. These changes are mainly caused by a weakening of index of proliferative activity. In animals that postoperatively received substitutive thyroxin hormonotherapy and courses of thymulin these disorders don't occur or they are not expressed significantly.
