Comparison of the effects of monastrol and oxomonastrol on human hepatoma cell line HepG2/C3A

Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investiga...

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Detalles Bibliográficos
Autores: Lilian Areal Marques, Simone Cristine Semprebon, Daniele Sartori, Ângelo de Fátima, Lúcia Regina Ribeiro, Mário Sérgio Mantovani
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Brasil
Institución:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:inglés
OAI Identifier:oai:repositorio.ufmg.br:1843/70470
Acceso en línea:https://doi.org/10.21873/anticanres.11434
http://hdl.handle.net/1843/70470
https://orcid.org/0000-0003-2344-5590
https://orcid.org/0000-0002-7550-8509
https://orcid.org/0000-0002-0465-9932
https://orcid.org/0000-0002-9857-8681
https://orcid.org/0000-0001-5268-6508
Access Level:acceso abierto
Palabra clave:Monastrol
Oxo-monastrol
Human hepatoma cell line
Anticancer activity
Morfologia
Química
Agentes antineoplásicos
Apoptose
Testes biológicos
Microscopia de fluorescência
Câncer - Quimioterapia
Descripción
Sumario:Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels. However, oxomonastrol was cytotoxic only at the highest concentrations used, without reducing cell proliferation and viability. Moreover, no genotoxic damage or alteration of levels of mRNA were found. Our results suggest that monastrol has greater antiproliferative activity compared to oxomonastrol, and this effect is probably related to the DNA damage induced by monastrol and its possible bioactivation demonstrated by the increase in CYP1A1 mRNA expression. Moreover, these effects appear to be related to the presence of the sulfur atom in its structure.