Efeito antimitótico de um derivado de pirimidinona no desenvolvimento embrionário de ouriços-do-mar

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Oliveira, Dalliane Macedo Lopes de
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraíba
Brasil
Biologia Celular e Molecular
Programa de Pós-Graduação em Biologia Celular e Molecular
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/9458
Resumo: Cancer is characterized by uncontrolled cell growth of a particular tissue, which invades and impairs healthy cells functions. Chemotherapy is the main cancer treatment, and consists of drug administration that interferes in several metabolic pathways, leading to cancer cell death. Among the main chemotherapy drugs, antimitotics directly affect cell division. This study aimed to investigate the effect of a pyrimidinone derivative (4-4-chloro-phenyl)-2-(-4-methoxy-phenyl)-6-oxo-1,6-dihydropyrimidine- 5-carbonitrile, Py-09) on embryonic development of the sea urchin Echinometra lucunter. Adult animals were collected at João Pessoa coast, Paraíba, Brazil and kept in filtered sea water under constant air flow. Gametes or embryos were treated with Py-09 and the effects of the compound were analyzed on fertilization, embryonic development, mitochondrial membrane potential (ΔΨm), production of reactive oxygen species (ROS) and ABC transporters activity. Py-09 (12.5 μM) inhibited around 60% fertilization of pretreated eggs. However, treatment of sperm with Py-09 did not affect fertilization rate. Treatment of zygotes with Py-09 inhibited the early embryonic development in a time and dose-dependent pattern, with the maximum effect at 50 μM (EC50 = 12.5 μM). Morphological changes were observed in the pattern of embryos cleavage (unequal cleavage) and at larval stages (irregular distribution and cracks of spicules and pigment cells leakage). Py-09 induced the loss of ΔΨm without altering ROS intracellular levels. The assays with ABCB1 and ABCC1 transporters inhibitors (Reversin 205 and MK571, respectively) showed that Py-09 is not ABC proteins substrate. The intracellular calcein accumulation assay and PY-09/vinblastine association demonstrated Py-09 was not able to increase intracellular calcein fluorescence levels and that the compound did not reverse MXR phenomenon. In summary, this study demonstrated that the Py-09 features a remarkable antimitotic activity, producing changes both in morphology and cell physiology. Further studies are needed for a better understanding of the mechanism of action of the compound, and research on the potential of Py-09 as pharmacological tool for in vitro studies, as well as its therapeutic use.