Studies on the expression of the GSH/GSSG redox system in HNSCC cells under consideration of the HPV status

Introduction: Head and neck squamous cell carcinomas (HNSCC) are the most prevalent malignancies of the upper aero-digestive tract. Resistance of HNSCC to radiotherapy hampers the efficacy of tumor treatment. The GSH/GSSG cellular redox buffer system is capable of neutralizing radicals such as radiation-induced reactive oxygen species thereby helping to protect tumor cells from therapy induced cell death. Material and methods: Three HPV negative and three HPV positive HNSCC cell lines were deployed in the study. HNSCC cells were photon-irradiated with 4 Gy. Measurement of total as well as reduced (GSH) and oxidized (GSSG) glutathione was done with the GSH/GSSG Glo™ Assay. MK571, an inhibitor of the glutathione transporter ABCC1, was applied in a concentration of 50 µmol/L. Results: A strong heterogeneity regarding the glutathione levels was noted between the individual cell lines, independent of irradiation, with on average, but not significantly, lower glutathione levels in the HPV^pos group. The HPV positive cell line UM-SCC-47 exhibited conspicuously low GSSG levels, which increased after treatment of cells with MK571. UT-SCC-26A, a known cisplatin resistant cell line, exhibited the highest amount of GSSG. The irradiated cell group exhibited significantly lower levels of total, reduced (GSH) and oxidized (GSSG) glutathione, whereas the GSH/GSSG ratio did not change significantly. Conclusion/Discussion: The observations point to major differences in the capability of HNSCC cells to fend of cytotoxic radicals, which are in accordance with our previous reports (Tonigold et al., J Cancer Res Clin Oncol, 2014). Further studies are needed to evaluate the interconnection of the GSH/GSSG redox system with ABC transporters such as ABCC1 and its role in therapy resistance.

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