Taste dysfunctions like bitter phantogeusia belong to the most prevalent chemotherapy-related side effects and impair the food intake and the nutritional status as well as the overall quality of life of patients. In order to enable the development of effective treatment strategies, the aim of this study was to elucidate the cellular and molecular mechanisms that are involved in the development of bitter phantogeusia during platinum (Pt)-based chemotherapy. For this purpose, we used human gastric tumour cells (HGT-1), functioning as a cellular model system (i) to identify bitter and bitter modulating compounds and (ii) to identify the involvement of bitter taste receptors (TAS2Rs). Our in vitro results demonstrate that cisplatin and carboplatin increased the bitterness response by HGT-1 cells, with cisplatin showing a stronger effect. Homoeriodictyol (HED), a bitter masking compound targeting various TAS2Rs, counteracted the cellular bitterness response caused by 50 µM cisplatin by -75 % ± 15 %, whereas the effect of 200 µM carboplatin was reduced by -76 % ± 11 %. Gene expression analysis revealed that expression levels of various TAS2Rs were altered due to Pt-based treatment. Finally, a functional role of the TAS2R5 in the HGT-1 bitterness response induced by the Pt-based drugs was verified by a siRNA knockdown approach. Along with data from cellular uptake studies carried out by means of ICP-MS, these results strongly support our hypothesis that Pt-based chemotherapeutics administered i.v. contribute to bitter phantogeusia experienced by cancer patients. Whether the administration of HED to cancer patients could help to reduce bitter phantogeusia and improve side effects like loss of appetite and body weight, has to be elucidated in a clinical study.

Funding: This research was funded by the Vienna Science and Technology Fund, grant number LS18-059.