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J Med Food ; 11(2): 230-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18598163

RESUMO

Luteolin has been shown to possess antitumorigenic, antioxidant, and anti-inflammatory properties. In the present study, we investigated the protective mechanism of luteolin against cisplatin-induced apoptosis in auditory (House Ear Institute-Organ of Corti 1 [HEI-OC1]) cells. Luteolin was found to induce the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Luteolin also activated the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, which plays an important role in the expression of HO-1. Luteolin protected the cells against cisplatin-induced apoptotic cell death. The protective effect of luteolin was abrogated by zinc protoporphyrin IX (ZnPP IX), an HO inhibitor, and antisense oligodeoxynucleotides against the HO-1 gene. Furthermore, pretreatment with luteolin inhibited the activation of caspase-3 and the mitochondrial dysfunction, and the effect of luteolin on the activation of caspase-3 disappeared in the presence of ZnPP IX or PD098059. These results demonstrate that the expression of HO-1 by luteolin is mediated by the ERK pathway, and also that the activating of HO-1 inhibits cisplatin-induced apoptosis in HEI-OC1 1 cells.


Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Heme Oxigenase-1/genética , Luteolina/farmacologia , Órgão Espiral/citologia , Animais , Caspase 3/metabolismo , Linhagem Celular Transformada , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/biossíntese , Camundongos , Oligonucleotídeos Antissenso/farmacologia , Órgão Espiral/enzimologia , Proteínas Proto-Oncogênicas c-bcl-2/genética
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