Freitas, Janaina Cristiana de Oliveira CrispimMiranda, Cleine Aglacy Nunes2025-07-242025-07-242018-09-17MIRANDA, Cleine Aglacy Nunes. Avaliação da atividade citotóxica in vitro e in silico de alcaloides de Erythrina velutina em células de câncer cervical imortalizadas pelo Papilomavirus Humano (HPV). Orientadora: Dra. Janaina Cristiana de Oliveira Crispim Freitas. 2018. 87f. Tese (Doutorado em Desenvolvimento e Inovação Tecnológica em Medicamentos) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2018.https://repositorio.ufrn.br/handle/123456789/64909Considering the high occurrence of cervical cancer in the world and the adverse effects of the available treatments, the studies involving plant properties are relevant to the new generation of therapies for this particular type of tumor. Erythrina velutina (EV) is a native plant of Brazil, popularly known as mulungu. Preparations based on the husks of mulungu are used in traditional medicine as a sedative, an anticonvulsant and in the treatment of sleep disorders. Among the classes of metabolites found in the genus, it is worth mentioning the occurrence of erythrin alkaloids in several species. In this study, the total alkaloids fraction of the leaves was obtained by acid-base extraction and analyzed by Gas Chromatography coupled to a Mass Spectrometer. Six erythrocyte alkaloids, erythrin, erythraline, erythradine, erythrocyte, cristamidine and oxo- erythraline were identified from the chromatographic analysis of the EV extract. Only erythraline and oxo-erythraline have been reported in this species. The total alkaloid fraction and the erythraline isolate were evaluated for cytotoxic properties in SiHa strain HPV16+cervical cancer. The isolated alkaloid has also been tested in peripheral blood mononuclear cells (PBMC) of healthy women. All cells were cultured in culture medium and incubated with different concentrations of the samples. Cell viability was quantified by the MTT assay and absorbance (570 nm) by an ELISA reader, in each experiment. Cell death was evaluated using propidium iodide and anexin staining and flow cytometry analyzes. Both the total alkaloid fraction of EV, and its isolated compound, erythraline, significantly inhibited (p <0.05) the growth of SiHa cells at time kinetics of 24 and 48 hours. There was also an increase in cell death in a dose-dependent manner through cytometric analysis. After treatment with erythraline, the cell viability assay showed that the inhibitory effects were consistent with the morphological changes observed under a light microscope in a dose-dependent manner. The results also suggest there is a tendency to stop the cell cycle of SiHa in the G2/M phase in the presence of erythraline. It was observed that the percentages of cell death increased after exposure to erythraline associated with z-VAD (caspase inhibitor). Regarding the action of erythraline on human PBMC, no cytotoxic effect was observed. Using an in silico assay, three possible antitumor targets of interactions with erythraline isolated alkaloid, Polyamine Oxidase (PAO), Pyruvate Kinase M2 (PKM2) and Tankirase (TANK) were found. Based on evaluations of in vitro cytotoxic action and in silico studies, total alkaloids of Erythrina velutina and its erythraline isolate, played an important role in cytotoxicity, cell death and exhibited potential targets for cervical cancer immortalized by HPV.pt-BRAcesso AbertoNeoplasias do colo do úteroCâncer cervicalAlcaloidesErytrina velutinaCitoxicidadedoctoralThesisCIENCIAS DA SAUDE