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Toxicology ; 301(1-3): 58-65, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22796345

RESUMO

8-Methoxypsoralen (8-MOP), a naturally occurring compound, is a potent modulator of epidermal cell growth and differentiation in combination with ultraviolet light. However, there is little information on 8-MOP contribution to cell apoptosis alone. In the study, we evaluated 8-MOP, independently of its photoactivation, induced apoptosis in human hepatocellular carcinoma HepG2 cells. And we provide a molecular explanation linking 8-MOP to induce apoptosis. In HepG2 cells, treatment with 8-MOP induced the cell apoptosis in both dose-dependent and time-dependent manners. IC(50) values of 8-MOP were 8.775, 5.398 µM for 48 and 72 h, respectively. Further study showed that 8-MOP decreased the procaspase-3, procaspase-8, and procaspase-9, increased the ratio of Bax/Bcl-2 and decreased the survivin. Moreover, 8-MOP decreased differentiated embryonic chondrocyte gene1 (DEC1). Overexpression of DEC1 antagonized partially apoptosis induced by 8-MOP. And overexpression of DEC1 abolished the decrease of survivin and the activation of caspase-3 induced by 8-MOP partially. So, down regulation of DEC1 is involved in 8-MOP-induced apoptosis in HepG2 cells. Here, it is demonstrated that DEC1 possesses anti-apoptotic effects in 8-MOP-treated HepG2 cells. The findings provide more of a basis for 8-MOP as an anti-tumor agent in cancer therapy.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Hepatocelular/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Neoplasias Hepáticas/tratamento farmacológico , Metoxaleno/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Concentração Inibidora 50 , Neoplasias Hepáticas/patologia , Metoxaleno/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Survivina , Fatores de Tempo
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