Cisplatin is an anti-cancer drug which is effective against several cancers, but also causes harmful side-effects, including ototoxicity and hearing loss. While cisplatin is a bifunctional compound that forms coordinate covalent bonds with both strands of DNA, recently investigated monofunctional platinum(II) compounds bind to only one DNA strand, and may activate different cell-death mechanisms. As several monofunctional platinum(II) compounds have anti-cancer properties, but could target different cell-death pathways, they could potentially have different and reduced side-effects. In this study, the HEI-OC1 auditory hybridoma cell line was used to investigate the ototoxicity of cisplatin and two monofunctional platinum(II) compounds, phenanthriplatin and pyriplatin. First, a colorimetric spectrophotometer assay was used to measure HEI-OC1 cell viability after treatment with cisplatin, phenanthriplatin, or pyriplatin. Next, a fluorescent flow-cytometric assay was used to measure ROS levels. Finally, a luminescent spectrophotometric assay was used to measure caspase-3/7 levels. My results show that at 24- and 48-hours post-treatment, cisplatin, phenanthriplatin, and pyriplatin had similar effects on cell viability. At 24-hours, ROS levels significantly increased for each compound, but at 48-hours, ROS levels were comparable to the control. At 24-hours, caspase-3/7 activity was significantly decreased for each treatment. At 48-hours, caspase-3/7 activity was elevated only for the cisplatin treatment and was not different than the control for both monofunctional compounds.
Advisor(s) or Committee Chair
Michael Smith, Ph.D.
Biochemistry | Biology | Cancer Biology
Johnston, Alexandra, "Ototoxicity of Cisplatin, Pyriplatin, and Phenathriplatin in the Auditory Hybridoma Cell Line, HEI-OC1" (2020). Mahurin Honors College Capstone Experience/Thesis Projects. Paper 841.