Luteolin Suppresses Cisplatin-Induced Apoptosis in Auditory Cells: Possible Mediation Through Induction of Heme Oxygenase-1 Expression

Abstract

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.

Kaempferol Suppresses Cisplatin-Induced Apoptosis Via Inductions of Heme Oxygenase-1 and Glutamate-Cysteine Ligase Catalytic Subunit in HEI-OC1 cells

“…Similar up-regulation of HO-1 production occurs in the presence of curcumin (37), chalcone (38) and naringenin-7-O-glucoside (39). In a previous study, we also found that piperine protects cells against cisplatin-induced apoptosis by up-regulating the expression of anti-oxidative genes through the Nrf2 transcription factor pathway (31).…”

“…Epicatechin can also inhibit cisplatin-induced apoptosis and intracellular ROS generation (30). In addition, the activity of HO-1 can suppress the apoptotic effect of cisplatin (31,32).…”

“…Arsenite induces HO-1 expression via the ERK and p38 pathways in chicken hepatoma cells (47), but inhibition of p38 has no effect on cadmium-and hemindependent HO-1 expression in HeLa cells (10). Luteolin activates the ERK pathway (32), while piperine activated the JNK pathway (31).…”

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

“…CoPPIX inhibits cisplatin-induced death in the HEI-OC1 auditory-derived cell line (Kim et al 2006a(Kim et al , 2009So et al 2006So et al , 2008Choi et al 2007Choi et al , 2008Choi et al , 2011Gao et al 2010). HO-1 expression has been reported in cochlear hair cells and stria vascularis following a variety of stressors, including noise stress, heat stress, and pharmacological induction (Fairfield et al 2004;Lopez et al 2008;Kim et al 2009;Matsunobu et al 2009;Fetoni et al 2010).…”

“…Pharmacological induction of HO-1 is protective against multiple stresses in many tissue types, including ischemia-reperfusion injury in liver and retina (Tsuchihashi et al 2007;Sun et al 2010). Several studies have demonstrated that inducers of HO-1 protect against cisplatin-induced death in the HEI-OC1 auditory cell line (Kim et al 2006a(Kim et al , 2009So et al 2006So et al , 2008Choi et al 2007Choi et al , 2008Choi et al , 2011Gao et al 2010). We have shown that HO-1 induction inhibits hearing loss and hair cell death caused by aminoglycoside antibiotics (Francis et al 2011).…”