| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 843.67 KB | Adobe PDF |
Authors
Abstract(s)
A descoberta da mauveína, por William Perkin, em 1856, marcou a indústria da síntese de corantes. Desde então, as cianinas têm vindo a ser sintetizadas com diversos fins, nomeadamente, como sensibilizadores fotográficos. As possíveis aplicações na medicina têm vindo a ser intensivamente estudadas, como é exemplo o tratamento de tecidos tumorais, com auxílio da terapia fotodinâmica, sugerindo que há uma ação predominante na produção de espécies reativas de oxigénio, induzindo o stress oxidativo nas células cancerígenas. As glutationas S-transferases são uma superfamília de enzimas multifuncionais ubiquitárias que desempenham um papel fundamental na resposta da célula ao stress oxidativo e são consideradas enzimas de destoxificação. As enzimas envolvidas na destoxificação podem desempenhar um papel importante na suscetibilidade ao cancro. Alguns polimorfismos dos genes das glutationas S-transferases, os genes GSTM1 e GSTT1, parecem constituir um fator de risco e têm sido associados a uma maior suscetibilidade ao cancro da mama.
O objetivo principal deste trabalho é efetuar um estudo preliminar sobre os efeitos das tiocarbocianinas com cadeia N-alquílica em células humanas. Para tal, utilizou-se um ensaio para estudar a viabilidade celular (ensaio de MTT) e analisou-se a expressão dos genes GSTM1 e GSTT1 por PCR em tempo real nas células epiteliais com carcinoma da mama (MCF-7), e em fibroblastos saudáveis da derme humana (NHDF), após incubação e recuperação com os compostos em estudo.
Os nossos resultados mostraram que as tiocarbocianinas estudadas, com cadeia N-alquílica, demonstraram maior toxicidade na linha celular MCF-7 em comparação com as NHDF. Estas tiocarbocianinas, também mostraram, entre os possíveis mecanismos de toxicidade, o envolvimento em processos que promovem o stress oxidativo às células.
The discovery of mauveine, by William Perkin in 1856, marked the synthesis of the dye industry. Since then, cyanines have been synthesized with different purposes in particular as photographic sensitizers. Possible applications in the medicine have been intensively studied, as for example the treatment of tumor tissues with the aid of photodynamic therapy, suggesting that there is a predominant action in the production of reactive oxygen species, inducing oxidative stress on cells cancer. Glutathione S-transferases constitute a super-family of ubiquitous, multifunctional enzymes, which play a central role in cell response to the oxidative stress and are considered detoxification enzymes. The enzymes involved in the detoxification may play a significant role in cancer susceptibility. Some polymorphisms present in glutathione S-transferases, GSTM1 and GSTT1 genes, appear to be a risk factor and have been linked to an increased susceptibility to breast cancer. The aim of this study was to perform a preliminary study on the effects of thiacarbocyanines with N-alkyl chain in human cells. For such, was used an assay for studying cell viability (MTT assay) and analyzed, GSTM1 and GSTT1 genes expression by real time PCR in the epithelial cells with breast carcinoma (MCF-7), and in normal human dermal fibroblasts (NHDF) after incubation and recovery with the test compounds. The results showed that the thiacarbocyanines studied with N-alkyl chain demonstrated higher toxicity in MCF-7 cell line comparing to NHDF. These cyanines have also showed a possible mechanism of toxicity, involving processes that promote oxidative stress to cells.
The discovery of mauveine, by William Perkin in 1856, marked the synthesis of the dye industry. Since then, cyanines have been synthesized with different purposes in particular as photographic sensitizers. Possible applications in the medicine have been intensively studied, as for example the treatment of tumor tissues with the aid of photodynamic therapy, suggesting that there is a predominant action in the production of reactive oxygen species, inducing oxidative stress on cells cancer. Glutathione S-transferases constitute a super-family of ubiquitous, multifunctional enzymes, which play a central role in cell response to the oxidative stress and are considered detoxification enzymes. The enzymes involved in the detoxification may play a significant role in cancer susceptibility. Some polymorphisms present in glutathione S-transferases, GSTM1 and GSTT1 genes, appear to be a risk factor and have been linked to an increased susceptibility to breast cancer. The aim of this study was to perform a preliminary study on the effects of thiacarbocyanines with N-alkyl chain in human cells. For such, was used an assay for studying cell viability (MTT assay) and analyzed, GSTM1 and GSTT1 genes expression by real time PCR in the epithelial cells with breast carcinoma (MCF-7), and in normal human dermal fibroblasts (NHDF) after incubation and recovery with the test compounds. The results showed that the thiacarbocyanines studied with N-alkyl chain demonstrated higher toxicity in MCF-7 cell line comparing to NHDF. These cyanines have also showed a possible mechanism of toxicity, involving processes that promote oxidative stress to cells.
Description
Keywords
Cianinas Ensaios de Viabilidade Celular Glutationas S-Transferases Stress Oxidativo