Proapoptotic effects of NF-κB on cisplatin-induced cell death in auditory cell line

Abstract

Conclusions. The findings suggest that nuclear factor (NF)-κB is activated by cisplatin and plays a proapoptotic role during cell death in the auditory cell line HEI-OC1. Objectives. Cisplatin is a very effective antineoplastic drug but in high doses it shows ototoxicity by inducing apoptosis of hair cells in the cochlea. NF-κB is a transcription factor regulating apoptosis in many organs and tissues. This study examined the role of NF-κB in the apoptotic pathway induced by cisplatin in the auditory cell line, HEI-OC1. Materials and methods. Apoptotic cell death was identified by measuring caspase 3 activity and immunostaining with anti-caspase 3 antibody after cisplatin treatment (50 µM) for 24 h. To investigate the role of NF-κB in apoptotic cell death, HEI-OC1 cells treated with 50 µM of cisplatin were immunostained with anti-NF-κB (p65) antibody. Two different NF-κB inhibitors, Bay 11-7085 and SN-50, were co-incubated with cisplatin (50 µM) for 24 h and caspase 3 activity was assayed. Results. Immunostaining with anti-caspase 3 antibody and caspase 3 assay showed that cisplatin induced apoptosis in HEI-OC1 cells. After cisplatin treatment, NF-κB (p65) was activated to translocate from the cytoplasm into the nucleus. Co-treatment with NF-κB inhibitors reduced the cisplatin-induced apoptosis of HEI-OC1 cells.

• Cisplatin
• auditory system
• NF-κB
• ototoxicity
• apoptosis
• caspase 3
• auditory cell line