Research paperHEI-OC1 cells as a model for investigating drug cytotoxicity

- We evaluated the response of HEI-OC1 cells to eight pharmacological drugs.
- Only two of them, cisplatin and tobramycin, induced significant cell death.
- APAP and other drugs decreased cell viability by affecting cell proliferation.
- Dexamethasone and gentamicin stimulated cell's autophagy.
- Neomycin, penicillin and streptomycin stimulated cell's senescence.

The House Ear Institute-Organ of Corti 1 (HEI-OC1) is one of the few, and arguable the most used, mouse auditory cell line available for research purposes. Originally proposed as an in vitro system for screening of ototoxic drugs, it has been used to investigate, among other topics, apoptotic pathways, autophagy and senescence, mechanism of cell protection, inflammatory responses, cell differentiation, effects of hypoxia, oxidative and endoplasmic reticulum stress, and expression of molecular channels and receptors. However, the use of different techniques with different goals resulted in apparent contradictions on the actual response of these cells to some specific treatments. We have now performed studies to characterize the actual response of HEI-OC1 cells to a battery of commonly used pharmacological drugs. We evaluated cell toxicity, apoptosis, viability, proliferation, senescence and autophagy in response to APAP (acetaminophen), cisplatin, dexamethasone, gentamicin, penicillin, neomycin, streptomycin, and tobramycin, at five different doses and two time-points (24 and 48 h), by flow cytometry techniques and caspase 3/7, MTT, Cytotoxicity, BrdU, Beclin1, LC3 and SA-β-galactosidase assays. We also used HEK-293 and HeLa cells to compare some of the responses of these cells to those of HEI-OC1. Our results indicate that every cell line responds to the each drug in a different way, with HEI-OC1 cells showing a distinctive sensitivity to at least one of the mechanisms under study. Altogether, our results suggest that the HEI-OC1 might be a useful model to investigate biological responses associated with auditory cells, including auditory sensory cells, but a careful approach would be necessary at the time of evaluating drug effects.