Search PubMed⌕ Search

Biomedical subjects

I G Svechnikova

Publications and source records attributed to I G Svechnikova.

15 recordsLinked to original sources
PubMed2004

Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells.

The histone deacetylase (HDAC) inhibitor 4-phenylbutyrate (4-PB) is a non-toxic compound that can induce differentiation and promote maturation of various types of malignant cells. In the present study we show that 4-PB inhibit glioma cell proliferation, induce apoptosis and decrease mRNA expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in a concentration-dependent manner. Proliferation of established rat glioma cell lines (RG2 and C6) in culture was significantly decreased after treatment with 4-PB (2-40 mM). Low concentrations of 4-PB (2-20 mM) induced cell differentiation followed by apoptosis, whereas higher concentrations of 4-PB (40 mM) induced cell necrosis. Also, low concentrations of 4-PB significantly decreased GAPDH mRNA expression in C6 and RG2 rat glioma cells, suggesting a link between decreased cell proliferation, energy consumption, and down-regulation of GAPDH gene expression. We have found that GAPDH mRNA expression is markedly increased in human glioblastoma tissues. Therefore, the novel effect of 4-PB described here may offer means to suppress growth of glioma cells by diminishing the key reaction in glycolysis as a therapeutic approach for cancer.

Animals↗
PubMed2001

Role of cystatin C and cysteine proteinases in the development of mouse LS-lymphosarcoma.

The growth of LS-lymphosarcoma in CBA mice was accompanied by a decrease in the content of the major extracellular inhibitor cystatin C in the tumor, plasma and, to a lesser extent, in tissues not involved in tumor process (liver and spleen). Cyclophosphamide in a dose of 50 mg/kg prolonged the life-span of animals and decreased tumor size by 80%. Cathepsin B and L activities in the tumor tissue increased by 3 and 7 times, respectively. Cystatin C content in the tumor tissue, spleen, and plasma also increased. Cystatin C assay in tumor tissue and plasma helps to predict the rate of tumor growth and to evaluate the efficiency of antitumor therapy.

Animals↗
PubMed2000

Cystatin C in LS lymphosarcoma and HA-1 hepatoma treated with Ukrain and cyclophosphamide and involvement of apoptosis.

The concentration of cystatin C, a cysteine proteinase inhibitor, was measured during the treatment of murine LS lymphosarcoma with cyclophosphamide and HA-1 murine hepatoma with the antitumor drug Ukrain. It was shown that concentrations of cystatin C were very low in both the tumor tissues studied (HA-1 hepatoma cells and LS lymphosarcoma); increased cystatin C concentrations were found only in Ukrain-treated murine hepatoma, suggesting the mechanism of antitumor effect of this drug. Cyclophosphamide treatment in LS lymphosarcoma did not influence the concentration of cystatin C in tumor cells. At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide. While the DNA from untreated LS lymphosarcoma was very homogenous and its molecular weight was high, the DNA from tumors of treated mice broke down, giving rise to the ladder figure characteristically produced by cells dying from apoptosis. Evidence was obtained that cyclophosphamide-induced tumor regression was effected by apoptosis.

Alkaloids↗
PubMed2000

Influence of Ukrain and cyclophosphamide administration on HA-1 murine hepatoma and LS lymphoma on aspartic proteinase cathepsin D.

Cathepsin D, the major lysosomal aspartyl proteinase and a mediator of interferon-gamma and tumor necrosis factor-alpha-induced apoptosis, was studied in murine models of LS lymphosarcoma treated by cyclophosphamide (possible apoptosis induction), and HA-1 hepatoma treated by Ukrain (positive antitumor effect). It was found that cyclophosphamide, as well as cyclophosphamide plus Ukrain, increased cathepsin D specific activity in mice with LS lymphosarcoma. Ukrain alone had no effect on cathepsin D activity in LS lymphosarcoma. In HA-1 hepatoma cells cathepsin D activity was not changed compared with intact normal murine liver (day 10) and activity decreased during tumor development (on day 12). Ukrain significantly increased cathepsin D activity in ascitic fluid (day 10) and had a tendency to increase cathepsin D activity in ascitic cells but not to the normal value.

Alkaloids↗
PubMed1998

Macrophage stimulation and antitumor effect of Ukrain.

It has previously been demonstrated that Ukrain administration (0.5 mg in mice of 20 g, five times) to A/Sn mice results in retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with untreated controls. In the present study Ukrain was tested as a macrophage stimulator in intact mice and animals with HA-1 hepatoma. There were no changes to the carbon particles phagocytosis rate in the case of a single administration of Ukrain to intact mice. Significant secretion of procathepsin B into ascitic fluid was shown in tumor mice as well as marker enzyme of macrophages beta-hexosaminidase activity, suggesting an influx of macrophages into ascites. Single Ukrain administration increased this index, and repeated drug injections were followed by a tendency to normalization of secretion. The cytolytic effect of Ukrain against tumor cells (as a result of macrophage stimulation) is the most probable mechanism of its antitumor action, but this suggestion needs further experimental evidence with special attention paid to the balance of proteinases and endogenous proteinase inhibitors.

Adjuvants, Immunologic↗
PubMed1998

The influence of Ukrain on the growth of HA-1 tumor in mice: the role of cysteine proteinases as markers of tumor malignancy.

The influence of Ukrain (exerting a malignotoxic effect in vivo according to Nowicky J.W. et al [1]) on the growth of Hepatoma A (HA-1) tumors in mice and cysteine proteinases as markers of tumor growth and malignancy was studied. Ukrain administration (0.5 mg per mice of 20 g, in each of 5 i.p. injections) resulted in a reproducible and significant retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with the untreated control. Repeated Ukrain administration to mice increased the number of macrophages in ascites, decreased the number of tumor cells, and concomitantly reduced the increased level of monocytes in peripheral blood. In ascitic cells the specific activity of cathepsin B was higher than in the intact liver and was not influenced by Ukrain; activity of cysteine proteinases studied in ascitic fluid was much higher than that in serum. Tumor growth was followed by a decrease in cathepsin B activity in the liver and serum at day 10. Ukrain administration has a tendency to normalize the disturbances of cathepsin B activity during tumor development. The cathepsin L activity changes in ascitic fluid were more impressive than those of cathepsin B, indicating the special role of this cysteine proteinase in HA-1 tumor growth and invasiveness. The role of cysteine proteinases as markers of tumor malignancy and invasiveness is discussed.

Alkaloids↗
PubMed1998

Study of the antitumor effect of Ukrain: the role of macrophage secretion of alpha-1-proteinase inhibitor.

The positive antitumor effect of Ukrain was shown following i.m. injection of a mixture of this drug with Krebs-2 carcinoma cells to CBA mice. The protective effect was suggested to be a result of the influx of macrophages into the site of Ukrain injection. In contrast, contralateral administration of Ukrain had a negative effect, confirming our hypothesis that Ukrain attracts cytolytic macrophages. In the murine HA-1 hepatoma model treated by single or repeated Ukrain injections, a moderate positive effect of Ukrain was related to increased macrophage (alpha-1-proteinase inhibitor (PI) secretion. The role of tumor cells and macrophages in the secretion of PI (the main inhibitor of serine proteinases) during tumor development is discussed.

Alkaloids↗
PubMed1998

[Regulation of liver cysteine proteinases during macrophagal stimulation and depression].

The lysosomal pathway of intracellular protein degradation involves the cooperative action of proteinases, among which cysteine proteinases cathepsin B and cathepsin L are particularly important. The hypothesis that the abnormal ratio of proteinases/proteinase inhibitors (i.e. higher activities of proteinases and lower activities of their inhibitors) results in uncontrolled proteolysis and cellular dysfunctions has been experimentally tested. Cathepsin B was used as a marker of macrophagal lysosomes and cathepsin L was employed as a marker of hepatocytic lysosomes. Zymosan stimulation of macrophages was shown to induce increased secretion of macrophagal lysosomal enzymes into blood during early zymosan administration, followed by higher rates of phagocytosis and labilization of lysosomes both of macrophages and hepatocytes labilization. Macrophagal depression induced by gadolinium chloride in rats was also accompanied by increased secretion of acid hydrolases into blood and labilization of macrophageal lysosomes, which reflects the lysosomotropic properties of the agent. Gadolinium chloride prevented zymosan stimulation of macrophages in the liver, but not in the spleen and lung. A new approach is proposed to evaluate the functional activity of hepatocytic lysosomes by the marker lysosomal enzymes of macrophages (cathepsin B) and hepatocytes (cathepsin L). Possible modes of regulation of endogenous proteinases are considered with special emphasis on the protective function of endogenous proteinase inhibitors secreted by macrophages simultaneously with cathepsin B and other cysteine proteinases.

Animals↗
PubMedDate not supplied

[Cysteine proteinases and their inhibitors in the development of mouse HA-1 hepatoma and antineoplastic therapy].

Development of murine HA-1 hepatoma was accompanied by increased activity of cathepsin B (in ascitic cells), cathepsin D (in ascitic fluid) and increased activity of procathepsin B. There were some changes of cysteine proteinases in liver and spleen, not involved directly into tumor growth. The most prominent changes included the decreased level of cysteine proteinase inhibitors cystatin C and stefin A in ascitic cells (and to a lesser degree in liver tissue). During tumor development serum cystatin C concentration decreased by 3-times compared to intact mice. Treatment by antitumor drug Ukraine increased life span of mice with HA-1 hepatoma (transplanted intravenously), decreased the increment of tumor weight. In ascite such treatment caused a decrease of number of tumor cells and an increase of number of macrophages. Ukraie (administered once or 5-times in a dose of 0.5 mg per mice) increased cystatin C level, revealing protective mechanism of action.

Alkaloids↗
PubMedDate not supplied

[The role of plasma high density lipoproteins as modulators of specific hormonal effect of hydrocortisone].

Hydrocortisone affected less distinctly the gene expression in rat liver slices as compared with the simultaneous effect of the hormone and blood plasma high density lipoproteins (HDL). These substances acted cooperatively and the phenomenon observed was not reproduced by means of individual components. The protein moiety of HDL, but not of lipid part of the molecule, was of importance in realization of the effect. Inhibitors of lysosomal proteinases (pepstatin, soy bean inhibitor of trypsin and iodoacetamide) as well as inhibitors of lysosomes intracellular translocation (colchicine and vinblastine) blocked completely the cooperative action of hydrocortisone and HDL. Hydrocortisone-dependent activation of chromatin and stimulation of genes expression led to an increase in the binding constant of acridine orange with DNA, while molar concentration of binding sites of the probe was practically unaltered. At the same time, simultaneous effect of hydrocortisone and HDL did not alter the constants for acridine orange binding but concentration of the probe binding sites with DNA was distinctly increased.

Acridine Orange↗
PubMedDate not supplied

[Cooperative effect of high density lipoproteins and adaptive hormones in chromatin activation in rat liver].

Fluorescent probing of rat liver chromatin with acridine orange (AO) and ethidium bromide was employed to investigate the rat liver chromatin activation under stress in vivo and in vitro. A significant increase of molar concentration of AO binding sites with chromatin in nuclei suspension was demonstrated after intensive physical exercises and partial hepatectomy. These results reveal chromatin activation under these stress conditions. For the first time the chromatin activation was shown to be a result of the cooperative effect of hydrocortisone and blood plasma high density lipoproteins (HDL). Both HDL2 and HDL3 contribute to this cooperative action. The increase of concentration of AO binding sites and simultaneous increase of the ratio of red to green fluorescence (alpha), which represents the amount of one-stranded nucleic acids, show that chromatin activation in this case is accompanied by the derepression of new genes and also by the enhanced expression of already functioning ones. Adrenaline did not change the amount of AO binding sites but increased index alpha. This evidences for the enhanced expression of already functioning genes. Hydrocortisone-dependent chromatin activation led to the increase of the binding constant of AO with DNA, while molar concentration of binding sites of the probe was practically unaltered. At the same time, cooperative effect of hydrocortisone and HDL did not alter the constants of AO binding, but the concentration of the probe binding sites with DNA was significantly increased.

Adaptation, Physiological↗
PubMedDate not supplied

[Change in histone proteins in rat liver chromatin during exposure of the animal to functional stress].

Pattern of rat liver histones at intensive physical exercises with preliminary injection of lysosomotropic drugs was studied by method of electrophoresis in PAAG. Elevation of the acetylated forms of histone H4 was revealed. The increased proteolysis of lysine-rich histones (H1, H2A, H2B) was shown in swimming rats previously stimulated by prodigiosan. The possible role of lysosomal proteinases of liver cells in mechanism of chromatine activation is discussed.

Animals↗