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1.
Molecules ; 18(6): 6620-62, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23743888

RESUMO

The indole nucleus is an important element of many natural and synthetic molecules with significant biological activity. This review covers some of the relevant and recent achievements in the biological, chemical and pharmacological activity of important indole derivatives in the areas of drug discovery and analysis.


Assuntos
Indóis/química , Descoberta de Drogas , Indóis/síntese química , Indóis/farmacologia , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química
2.
Sci Rep ; 5: 8587, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25715710

RESUMO

In this study, we assessed the role of different reactive oxygen species (ROS) generated by soft jet plasma and chemical-induced ROS systems with regard to cell death in T98G, A549, HEK293 and MRC5 cell lines. For a comparison with plasma, we generated superoxide anion (O2(-)), hydroxyl radical (HO·), and hydrogen peroxide (H2O2) with chemicals inside an in vitro cell culture. Our data revealed that plasma decreased the viability and intracellular ATP values of cells and increased the apoptotic population via a caspase activation mechanism. Plasma altered the mitochondrial membrane potential and eventually up-regulated the mRNA expression levels of BAX, BAK1 and H2AX gene but simultaneously down-regulated the levels of Bcl-2 in solid tumor cells. Moreover, a western blot analysis confirmed that plasma also altered phosphorylated ERK1/2/MAPK protein levels. At the same time, using ROS scavengers with plasma, we observed that scavengers of HO· (mannitol) and H2O2 (catalase and sodium pyruvate) attenuated the activity of plasma on cells to a large extent. In contrast, radicals generated by specific chemical systems enhanced cell death drastically in cancer as well as normal cell lines in a dose-dependent fashion but not specific with regard to the cell type as compared to plasma.


Assuntos
Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Trifosfato de Adenosina/metabolismo , Apoptose , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica , Células HEK293 , Histonas/genética , Histonas/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Oxirredução , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Nitrogênio/farmacologia , Regulação para Cima , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
3.
Sci Rep ; 5: 8726, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-25735798

RESUMO

In this study, we show the selective and efficient anti-cancer effects of plasma (at a low dose) when cell metabolic modifiers are also included. 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor, was used with effective doses of non-thermal plasma, synergistically attenuating cell metabolic viability and inducing caspase-dependent and independent cell death. The combination treatment decreased the intracellular ATP and lactate production in various types of blood cancer cells in vitro. Taken together, our findings suggest that 2-DG enhances the efficacy and selectivity of plasma and induces the synergistic inhibition of cancer cell growth by targeting glycolysis and apoptosis. Specifically, this treatment strategy demonstrated an enhanced growth inhibitory effect of plasma in the presence of a metabolic modifier that was selective against cancer cells, not non-malignant cells. This is the first study to report the advantage of combining plasma with 2-DG to eradicate blood cancer cells. Finally, we conclude that 2-DG with non-thermal plasma may be used as a combination treatment against blood cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Desoxiglucose/farmacologia , Glicólise/efeitos dos fármacos , Gases em Plasma/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Caspases/genética , Caspases/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Camundongos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células U937
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