RESUMO
MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness.
Assuntos
Neoplasias da Mama/genética , Mama/patologia , Carcinoma Ductal de Mama/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Invasividade Neoplásica/patologiaRESUMO
The marine environment is a rich source of biological active compounds and the sponges can be considered the most productive one. This diversity gives rise to unique chemical compounds with potential pharmacological properties. Our study is focused on the genotoxic and antigenotoxic evaluation of two crude extracts obtained from the Brazilian endemic marine sponge Arenosclera brasiliensis. Salmonella typhimurium reverse mutation test with TA97, TA98, TA100 and TA102 strains were performed. For antimutagenic analysis, a pre-, co-, and post-treatment to evaluate, respectively, intracellular and extracellular reactions and possible modulation on DNA repair. Additionally, in order to verify the influence of the crude extracts on DNA damage induction, a plasmid-DNA treatment was assayed. No mutagenicity was observed in Salmonella reverse mutation test, neither DNA strand induced damage. Antimutagenic activity was observed in pre-, co-, and post-treatment. A significant antigenotoxic effect was observed in the crude extract, which suggests that A. brasiliensis extract has the potential to protect DNA from the action of 4NQO, 2-aminofluorene, sodium azide and mitomycin C.
Assuntos
Antimutagênicos/toxicidade , Poríferos/química , Salmonella typhimurium/efeitos dos fármacos , Animais , Antimutagênicos/isolamento & purificação , Brasil , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/isolamento & purificação , Mutagênicos/toxicidade , Plasmídeos/metabolismo , Salmonella typhimurium/genética , Extratos de TecidosRESUMO
The marine environment is a rich source of biologically active compounds with pharmacological properties. Marine organisms often produce secondary metabolites with structural features different from those produced by terrestrial ones, and the Phylum Porifera seems to be one of the most productive in this sense. This study was undertaken to provide data on mutagenic and antimutagenic activities from an acetone (Areac) and an ethanol (Areet) extract obtained from Arenosclera brasiliensis, an endemic Brazilian sponge. A qualitative Salmonella reverse mutation test was performed with the TA97, TA98, TA100, and TA102 strains by incubating cells with Areac and Areet in the presence and absence of a known mutagen. A cytotoxic evaluation of the extracts was also performed. A. brasiliensis did not display any mutagenic activity, but Areac showed significant toxicity against test strains. In the antimutagenic assay, a reduction in the number of his+ revertants was observed for the TA97, TA100 and TA102 strains treated with Areac when compared to the positive controls. Areet treatment showed protective activity against DNA lesions only for the TA100. These results are in agreement with those obtained previously with other A. brasiliensis extracts, suggesting an antimutagenic activity.
Assuntos
Antimutagênicos/farmacologia , Citotoxinas/farmacologia , Extratos Vegetais/farmacologia , Poríferos/química , Salmonella typhimurium/efeitos dos fármacos , Acetona/química , Animais , Etanol/química , Viabilidade Microbiana/efeitos dos fármacos , Testes de Mutagenicidade , Salmonella typhimurium/genética , Salmonella typhimurium/crescimento & desenvolvimentoRESUMO
The marine environment is a rich source of biologically active compounds with pharmacological properties. Marine organisms often produce secondary metabolites with structural features different from those produced by terrestrial ones, and the Phylum Porifera seems to be one of the most productive in this sense. This study was undertaken to provide data on mutagenic and antimutagenic activities from an acetone (Areac) and an ethanol (Areet) extract obtained from Arenosclera brasiliensis, an endemic Brazilian sponge. A qualitative Salmonella reverse mutation test was performed with the TA97, TA98, TA100, and TA102 strains by incubating cells with Areac and Areet in the presence and absence of a known mutagen. A cytotoxic evaluation of the extracts was also performed. A. brasiliensis did not display any mutagenic activity, but Areac showed significant toxicity against test strains. In the antimutagenic assay, a reduction in the number of his+ revertants was observed for the TA97, TA100 and TA102 strains treated with Areac when compared to the positive controls. Areet treatment showed protective activity against DNA lesions only for the TA100. These results are in agreement with those obtained previously with other A. brasiliensis extracts, suggesting an antimutagenic activity.
Assuntos
Animais , Antimutagênicos/farmacologia , Citotoxinas/farmacologia , Extratos Vegetais/farmacologia , Poríferos/química , Salmonella typhimurium , Acetona/química , Etanol/química , Testes de Mutagenicidade , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/genética , Viabilidade MicrobianaRESUMO
Toxicity of an alcohol-free hydro-alcoholic grape skin extract (GSE) obtained from red grapes Vitis labrusca (Isabel varietal) that present antihypertensive, vasodilator and antioxidant effects was estimated by different bioassays. Using the Salmonella/microsome assay for strains TA97, TA98, TA100 and TA102 no mutagenicity was detected for all tested concentrations (0.1-100 microg/ml), even with metabolization. Nevertheless, cytotoxicity was observed for TA97 and TA102 with and without metabolization and for TA100 with metabolization. The measurement of beta-galactosidase induction in the SOS-chromotest was positive only for Escherichia coli PQ37 when metabolization enzymes were present. Using Balb/c 3T3 fibroblasts, DNA strand breaks induction by GSE was also investigated by the comet assay and no significative difference was detected for treated and no treated DNA for 60 min. Our data suggest that GSE although no mutagenic presents cytotoxic activity.