Aproveitamento de Resíduos da Agroindústria Cítrica para Investigação de Moléculas com Atividade Antiproliferativa em Células de Adenocarcinoma Gástrico (AGS)

• Ano de defesa: 2024
• Autor(a) principal: Polese, Jullia Ramos de Sousa
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Química; Centro de Ciências Exatas; UFES; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Câncer gástrico; Citrus; Eriocitrina; Flavanonas; Hesperidina; subject.br-rjbn; Ciências exatas e da Terra/Química/Química Orgânica/ Quíica dos Produtos Naturais
• Link de acesso: http://repositorio.ufes.br/handle/10/17394

Citrus farming is one of the most common agricultural activities in tropical and subtropical countries. However, approximately half of the total citrus fruit production is transformed into waste with a high organic matter content. These residues are rich in flavonoids, especially flavanones, which have been studied for their medicinal properties, including their use in the management of gastric cancer. Extracts from peels and pomace of citrus species consumed in the State of Espírito Santo, Brazil, were subjected to cytotoxicity tests on gastric adenocarcinoma cells (AGS) and macrophages (RAW 264.7) with the aim of selecting those with a greater possibility of use in patients with gastric cancer. The chemical similarity between them was evaluated using mass spectrometry data (ESI-FT-ICR MS) subjected to principal component analysis and liquid chromatography coupled to mass spectrometry (UPLCMS). ESI (-) FT-ICR MS made it possible to identify the presence of the flavanone’s hesperidin, eriocitrin, narirutin, hesperetin, eriodictyol, and naringenin. Cytotoxic evaluation by the MTT method showed considerable antiproliferative activity for samples of Tahiti lemon pomace extract (IC50 = 38,44 ± 0,82 μg/mL) and no toxicity in macrophages (IC50 > 800 μg/mL) at the doses tested. Tahiti lemon peel extract was considered cytotoxic to AGS (IC50 = 59,04 ± 1,06 μg/mL), but also showed cytotoxicity to RAW 264.7 macrophages (IC50 = 296,2 ± 0,13 μg/mL). The UPLC-MS technique made it possible to distinguish compounds from the flavonoid, coumarin, and limonoid classes in the Tahiti lemon peel extract sample that were not present in the pomace extract sample. The antiproliferative activity was mainly related to the presence of the flavanone’s hesperidin and eriocitrin, although samples of other citrus residues containing only hesperidin also showed antiproliferative activity at higher concentrations. To justify this hypothesis regarding the antiproliferative activity of flavanones, in silico studies were conducted on thymidylate synthase (TS) and hydroxymethylglutayl-CoA reductase (HMGCR), which are overexpressed in AGS cells. Both flavanones showed excellent anchoring in the effective sites of the enzymes, corroborating the hypothesis raised. Based on the study carried out, Tahiti lemon residues, as well as other citrus sources, can be considered promising raw materials to generate new materials for the management of gastric cancer.