RESUMO
The results of the study of the effect of a mononuclear dinitrosyl iron complex (DNIC7) with functional sulfur-containing ligands (NO donors) on the viability of multiple myeloma cells are presented. It was shown that DNIC7 decreased cell viability and inhibited the proliferation of multiple myeloma cells, i.e., exhibits cytotoxic properties. Fluorescent analysis showed that the DNIC7 compound decreases the level of intracellular glutathione and increases the level of reactive oxygen species in multiple myeloma cells. It is assumed that DNIC7 has a therapeutic potential for the treatment of cancer.
Assuntos
Antineoplásicos/farmacologia , Ferro/farmacologia , Mieloma Múltiplo/patologia , Óxidos de Nitrogênio/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The results of the study of the effect of mononuclear dinitrosyl iron complexes (DNICs) with functional sulfur-containing ligands (NO donors) on the cell viability and metabolism of human lung fibroblasts are presented, and the efficiency of their action is evaluated. It was shown that cationic DNICs increased the cell viability of fibroblasts and demonstrated the cytoprotective properties. Fluorescent analysis revealed that the DNICs compounds decrease the mitochondrial membrane potential but do not have a significant effect on the level of glutathione and reactive oxygen species in fibroblasts. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases.
Assuntos
Fibroblastos/metabolismo , Ferro/farmacologia , Pulmão/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Óxidos de Nitrogênio/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Pulmão/patologiaRESUMO
The effect of synthetic analogues of dinitrosyl mononuclear iron complexes (DNICs) with functional sulfur-containing ligands (NO donors) on the activity of myeloperoxidase (MPO) was studied, and their efficiency was evaluated. It was shown that the enzyme MPO is the molecular target of DNICs. It was found that six DNICs inhibited the activity of MPO and one compound potentiated it. The evaluation of their efficiency showed that two DNICs effectively inhibited the activity of MPO by 50% at IC50 = 2 × 10-4 M and IC50 = 5 × 10-7 M.
Assuntos
Ferro/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Óxidos de Nitrogênio/farmacologia , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , RatosRESUMO
In this work the effect of RHAMM (receptor hyaluronan-mediated motility)-target peptides was investigated on the viability, apoptosis and necrosis of prostate cancer cells (PC3m-LN4). It has been established that RHAMM-target peptides inhibited on 90 % cell viability of PC3m-LN4 cells at a concentration of 10 ug / ml (2Ñ 10-7 M) for 48 h. It has shown that RHAMM-target peptides induced apoptosis and inhibited necrosis of tumor cells. RHAMM-target peptide had no effect on fibroblasts (non-tumor cells) and fibroblasts (RHAMM-/-). The studies also revealed that RHAMM-target peptides enhanced activity of caspase-3/7 in cancer cells.
Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas da Matriz Extracelular/genética , Receptores de Hialuronatos/genética , Peptídeos/administração & dosagem , Neoplasias da Próstata/genética , Apoptose/efeitos dos fármacos , Caspase 3/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proteínas da Matriz Extracelular/administração & dosagem , Fibroblastos/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/administração & dosagem , Masculino , Peptídeos/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , TransfecçãoRESUMO
In this paper we investigated the effect of RHAMM-target peptides on the invasion of breast cancer cells (MDA-MB-231). Cells were plated on gelatin substrate, Cy3-fluorescein-labeled, and then simultaneously processed with RHAMM-target peptides. Invasion of the cells was assessed by quantitative analysis of the area degradation of gelatin, using ImageJ software. We have found that RHAMM-target peptides inhibited the invasion of tumor cell by - 80% at a concentration of 10µg/ml (2x10â»7 M). By confocal microscopy we also showed that a population of cancer cells was heterogeneous and composed from small cells (invasive) and large cells, non-invasive cells with 4-5 nucleus in the cytoplasm. We found that treatment of cells with RHAMM-target peptides led to a decrease in the number of cells of large size and induced structural disorganization of actin and enhanced amount of stress-fibers of actin.
