Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity

Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells.

House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests.

LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively.

LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses.