Banca de DEFESA: CLEINE AGLACY NUNES MIRANDA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : CLEINE AGLACY NUNES MIRANDA
DATA : 17/09/2018
HORA: 14:00
LOCAL: Auditório CCS
TÍTULO:

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PALAVRAS-CHAVES:

Cervical cancer; Alkaloids; Erytrina velutina; Cytotoxicity; In silico

PÁGINAS: 132
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Considering the high occurrence of cervical cancer in the world and the adverse effects of the
available treatments are relevant the studies involving vegetal assets to the generation of new
therapies for this type of tumor. Erythrina velutina (EV) is a plant native to Brazil popularly
known as mulungu. Preparations based on the husks of mulungu are used in traditional
medicine as a sedative, 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 leaves was obtained by
acid-base extraction and analyzed by Gas Chromatography coupled to Mass Spectrometer. Six
erythrocyte alkaloids, erythrin, erythraline, erythradine, erythrocyte, cristamidine and oxo
erythraline were identified in the chromatographic analysis of the EI extract, with only eritralin
and oxo erythraline being reported in this species. The total alkaloid fraction and the eritralin
isolate were evaluated for cytotoxic properties in cervical cancer strain SiHa HPV16 +. Cells
were cultured in culture medium and incubated with different concentrations of the samples.
Cell viability was quantitated by the MTT assay and absorbance (570 nm) by an ELISA reader
in each experiment. Cell death was evaluated using Propidium and Annexin Iodide 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 the 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 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 of cells with erythralin associated with caspase-dependent z
VAD (caspase inhibitor). Regarding the action of Erythraline in normal cells, it did not present a
cytotoxic effect in human peripheral blood mononuclear cells. Three possible antitumor targets
of interactions with the isolated erythraline alkaloid were found by in silico assay. Based on
assays to evaluate cytotoxic action and in vitro studies, the total alkaloids of Erythrina velutina
and its isolated Erythralin played an important role in cytotoxicity, cell death and exhibited
potential targets for cervical cancer immortalized by HPV.

MEMBROS DA BANCA:
Presidente - 3313589 - JANAINA CRISTIANA DE OLIVEIRA CRISPIM FREITAS
Interno - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Externo ao Programa - 1804884 - VIVIAN NOGUEIRA SILBIGER
Externo à Instituição - EDUARDO ANTÔNIO DONADI - USP
Externo à Instituição - NORMA LUCENA SILVA - Fiocruz - PE