Luteolin suppresses cisplatin-induced apoptosis in auditory cells: possible mediation through induction of heme oxygenase-1 expression.
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.
Choi
Byung-Min
BM
Vestibulocochlear Research Center and Department of Biochemistry, School of Medicine, Wonkwang University, Iksan, Chonbuk, Republic of Korea.
Lim
Dai-Won
DW
Lee
Ju-A
JA
Gao
Shang Shang
SS
Kwon
Dae Young
DY
Kim
Bok-Ryang
BR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009925:Organ of Corti / Q000166:cytology* / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D047311:Luteolin; D002945:Cisplatin