Publicação
Lectins in Mediterranean flora: Proteomics and antitumoral activity in colon cancer cells
| Resumo: | Lectins are proteins capable of specifically binding to glycans. This characteristic makes them unique molecules in cell recognition, especially of anomalous cells, since they have on their surface characteristic receptors. In addition to being of extreme importance in cell recognition, lectins have been described as capable of inducing cell death in various types of cancer, through several processes, namely, apoptosis and autophagy. Thus, because lectins are widely distributed in nature, with plants being one of the largest reservoirs, and have particular characteristics, these proteins are a topic of intense research. Colorectal cancer is the third most common cancer in men and the second most common in women. Phenotypic changes may be due to post-translational modifications, namely, changes in protein glycosylation, more specifically in N-glycosylation. N-glycans are of extreme importance in tumorigenesis, since they are involved in several cellular mechanisms, such as metabolization, signaling, growth, cell adhesion, cell-matrix interaction, invasion and metastasis. The studies presented in this thesis aimed to discovery new lectins, present in Mediterranean flora species, with capacity to specifically interact with colorectal cancer cells and induce cell death. After protein separation of lectins present in the protein extracts of the selected species, Arbutus unedo, it was found that the protein of interest appears to have a molecular weight of ≈ 15 kDa, being able to interact with HT29 human colon cancer cell membranes. In antitumor activity assays in HT29 cells, the purified protein increased cell death and decreased cell viability. However, when compared to the protein extract, the purified protein showed less activity in both assays. Caspases-3/7 activity assays and nuclear fragmentation assays suggest that cell death may not occur through apoptosis under these experimental conditions. In conclusion, we show the presence of lectins in the studied species, and the purified lectin demonstrated binding capacity and antitumor activity for the HT29 cells. |
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| Autores principais: | Oliveira, Isabel Castelo Branco |
| Assunto: | Lectinas Cancro colon retal Glicosilação aberrante Apoptose Necrose Teses de mestrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Lectins are proteins capable of specifically binding to glycans. This characteristic makes them unique molecules in cell recognition, especially of anomalous cells, since they have on their surface characteristic receptors. In addition to being of extreme importance in cell recognition, lectins have been described as capable of inducing cell death in various types of cancer, through several processes, namely, apoptosis and autophagy. Thus, because lectins are widely distributed in nature, with plants being one of the largest reservoirs, and have particular characteristics, these proteins are a topic of intense research. Colorectal cancer is the third most common cancer in men and the second most common in women. Phenotypic changes may be due to post-translational modifications, namely, changes in protein glycosylation, more specifically in N-glycosylation. N-glycans are of extreme importance in tumorigenesis, since they are involved in several cellular mechanisms, such as metabolization, signaling, growth, cell adhesion, cell-matrix interaction, invasion and metastasis. The studies presented in this thesis aimed to discovery new lectins, present in Mediterranean flora species, with capacity to specifically interact with colorectal cancer cells and induce cell death. After protein separation of lectins present in the protein extracts of the selected species, Arbutus unedo, it was found that the protein of interest appears to have a molecular weight of ≈ 15 kDa, being able to interact with HT29 human colon cancer cell membranes. In antitumor activity assays in HT29 cells, the purified protein increased cell death and decreased cell viability. However, when compared to the protein extract, the purified protein showed less activity in both assays. Caspases-3/7 activity assays and nuclear fragmentation assays suggest that cell death may not occur through apoptosis under these experimental conditions. In conclusion, we show the presence of lectins in the studied species, and the purified lectin demonstrated binding capacity and antitumor activity for the HT29 cells. |
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