The monofunctional platinum(II) compounds, phenanthriplatin and pyriplatin, modulate apoptosis signaling pathways in HEI-OC1 auditory hybridoma cells.

The monofunctional platinum(II) compounds, phenanthriplatin and pyriplatin, modulate apoptosis signaling pathways in HEI-OC1 auditory hybridoma cells. Neurotoxicology. 2020 May 13;: Authors: Monroe JD, Johnston AM, Smith ME Abstract Cisplatin is a platinum(II) chemotherapy drug that can cause the side-effect of ototoxicity and hearing loss. The monofunctional platinum(II) complexes, phenanthriplatin and pyriplatin, have recently been investigated as anti-cancer agents but their side-effects are largely unknown. Here, we used the auditory hybridoma cell line, HEI-OC1, to investigate the ototoxicity of cisplatin, phenanthriplatin and pyriplatin. The effect of these compounds against cellular viability, on reactive oxygen species (ROS) production, mitochondrial membrane polarization, caspase-3/7 activity, DNA integrity and caspase-12 expression were measured using spectrophotometric, flow cytometric and blot analyses. We found that the monofunctional complexes and cisplatin decreased cellular viability. All three compounds increased ROS yield at 24 hours, but at 48 hours, ROS levels returned to normal. Also, the compounds did not depolarize the mitochondrial membrane. All three compounds reduced caspase-3/7 activity at 24 hours; cisplatin increased caspase-3/7 activity and caused apoptosis at 48 hours. Caspase-12 expression was associated with all three compounds. In summary, the monofunctional complexes may cause ototoxicity li...
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research