Uma breve revisão sobre o efeito da manose em células tumorais
Data
2022-07-28
Autores
Oliveira, Luísa Martins de Moura [UNIFESP]
Orientadores
Ferreira, André Zelanis Palitot [UNIFESP]
Tipo
Trabalho de conclusão de curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Durante o desenvolvimento tumoral, as células cancerígenas passam por uma série de modificações que fornecem capacidades específicas de proliferação e sobrevivência, incluindo alterações no metabolismo celular. As mudanças induzidas nas vias metabólicas possuem papel fundamental para a compreensão do estabelecimento e da progressão do câncer, e, portanto, seu entendimento permite encontrar tratamentos alternativos que atuem de maneira eficaz contra a doença, como é o caso do tratamento das células tumorais com manose. A manose é um epímero da glicose, característica que permite com que os dois monossacarídeos sejam transportados pelos mesmos transportadores de membrana. Diversos pesquisadores demonstraram que linhagens tumorais distintas apresentam respostas variáveis ao tratamento com manose, dependendo dos níveis de expressão da enzima fosfomanose isomerase (PMI). Linhagens que apresentam baixos níveis de PMI tendem a ser mais sensíveis à manose do que linhagens com altos níveis, o que pode ser justificado pelo acúmulo de manose-6-fosfato no interior das células, que tem ação inibitória contra as enzimas hexoquinase, fosfoglicose-isomerase (PGI) e glicose-6-fosfato desidrogenase, envolvidas com o metabolismo da glicose. Neste trabalho, foi feita uma revisão bibliográfica acerca dos efeitos causados em células tumorais com o monossacarídeo manose, bem como as vias metabólicas e os mecanismos bioquímicos afetados durante o processo tumorigênico. Para tal, foram selecionados 45 artigos científicos em bases de dados como PubMed, Elsevier, Scielo e Google Scholar, utilizando como critério a credibilidade da busca e a robustez de informações existentes. Foi feita uma descrição dos resultados e discussão das hipóteses, e por fim, uma análise crítica foi feita para contribuir com a conclusão e indicação de perspectivas futuras. Observou-se que o uso da manose demonstrou ser uma alternativa promissora para a supressão do crescimento de tumores e para aumentar a atividade de agentes quimioterápicos, apresentando resultados positivos a partir do uso de modelos animais e quanto à segurança de utilização em concentrações pré-determinadas.
During tumor development, cancer cells undergo a series of modifications that provide specific proliferation and survival capabilities, including changes in cellular metabolism. Changes induced in metabolic pathways play a fundamental role in understanding the establishment and progression of cancer, and therefore, their understanding allows finding alternative treatments that act effectively against the disease, such as the treatment of tumor cells with mannose. Mannose is an epimer of glucose, a characteristic that allows the two monosaccharides to be transported by the same membrane transporters. Several researchers have demonstrated that different tumor strains show variable responses to mannose treatment, depending on the expression levels of the enzyme phosphomannose isomerase (PMI). Lines with low levels of PMI tend to be more sensitive to mannose than lines with high levels, which can be explained by the accumulation of mannose-6-phosphate inside the cells, which has an inhibitory action against hexokinase, phosphoglucose- isomerase (PGI) and glucose-6-phosphate dehydrogenase, involved in glucose metabolism. In this work, a literature review was carried out on the effects caused in tumor cells with the monosaccharide mannose, as well as the metabolic pathways and biochemical mechanisms affected during the tumorigenic process. To this end, 45 scientific articles were selected in databases such as PubMed, Elsevier, Scielo and Google Scholar, using as criteria the credibility of the search and the robustness of existing information. A description of the results and discussion of the hypotheses were made, and finally, a critical analysis was made to contribute to the conclusion and indication of future perspectives. It was observed that the use of mannose proved to be a promising alternative for the suppression of tumor growth and to increase the activity of chemotherapeutic agents, showing positive results from the use of animal models and regarding the safety of use in predetermined concentrations.
During tumor development, cancer cells undergo a series of modifications that provide specific proliferation and survival capabilities, including changes in cellular metabolism. Changes induced in metabolic pathways play a fundamental role in understanding the establishment and progression of cancer, and therefore, their understanding allows finding alternative treatments that act effectively against the disease, such as the treatment of tumor cells with mannose. Mannose is an epimer of glucose, a characteristic that allows the two monosaccharides to be transported by the same membrane transporters. Several researchers have demonstrated that different tumor strains show variable responses to mannose treatment, depending on the expression levels of the enzyme phosphomannose isomerase (PMI). Lines with low levels of PMI tend to be more sensitive to mannose than lines with high levels, which can be explained by the accumulation of mannose-6-phosphate inside the cells, which has an inhibitory action against hexokinase, phosphoglucose- isomerase (PGI) and glucose-6-phosphate dehydrogenase, involved in glucose metabolism. In this work, a literature review was carried out on the effects caused in tumor cells with the monosaccharide mannose, as well as the metabolic pathways and biochemical mechanisms affected during the tumorigenic process. To this end, 45 scientific articles were selected in databases such as PubMed, Elsevier, Scielo and Google Scholar, using as criteria the credibility of the search and the robustness of existing information. A description of the results and discussion of the hypotheses were made, and finally, a critical analysis was made to contribute to the conclusion and indication of future perspectives. It was observed that the use of mannose proved to be a promising alternative for the suppression of tumor growth and to increase the activity of chemotherapeutic agents, showing positive results from the use of animal models and regarding the safety of use in predetermined concentrations.