Presentation Details
Homoeriodictyol Counteracts the Bitterness Response Elicited by Pt-based Chemotherapeutics in a Cellular Model System and Reduces Bitter Phantogeusia in Cancer Patients

Sofie Zehentner1, 2, Agnes Mistlberger-Reiner1, Elisabeth Wachter3, Katja Bacovsky1, Michelle Friedrich3, Philip Pirkwieser4, Noreen Orth4, Valerie Boger4, Kristin Kahlenberg4, Johanna Kreißl4, Petra Rust3, Sophie Pils5, Christoph Grimm5, Jakob Ley6, Veronika Somoza1, 4, 7.

1Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.2Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna, Austria.3Department of Nutritional Sciences, University of Vienna, Vienna, Austria.4Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany.5Department of General Gynecology and Gynecologic Oncology, Comprehensive Cancer Center Vienna, Gynecologic Cancer Unit, Medical University of Vienna, Vienna, Austria.6Symrise AG, Research & Technology Flavors Division, Holzminden, Germany.7Chair of Nutritional Systems Biology, School of Life Science, Technical University of Munich, Freising, Germany

Abstract


Chemotherapy often causes taste dysfunctions, affecting patients’ food intake and quality of life. A multifactorial etiology of taste dysfunctions has been hypothesized, but the role of bitter taste receptors (TAS2Rs) is relatively unclear, and effective treatments for increased bitter taste sensitivity and bitter phantogeusia are missing. We investigated the underlying mechanisms of Pt-based chemotherapeutics in human parietal cells (HGT-1), a cellular surrogate model of TAS2R-linked bitter response. The bitter-masking flavor compound homoeriodictyol (HED), an antagonist for several TAS2Rs, was used to counteract these effects. Our results show that cisplatin (5 – 50 µM) and carboplatin (50 – 750 µM) elicit a dose-dependent bitterness response in HGT-1 cells, albeit to different extents, while 200 µM HED counteracts the bitterness response caused by 50 µM cisplatin by -75 ± 15% and the effect of 200 µM carboplatin by -76 ± 11%. The functional role of specific TAS2Rs in the bitter response induced by Pt-based drugs was confirmed by using corresponding HGT-1 kd or ko cells. In addition, a clinical pilot trial was conducted on ovarian cancer patients receiving a carboplatin-based chemotherapy. Hereby, an increased bitter taste sensitivity indicated by a lower recognition threshold of caffeine was reported in a sensory study. These results support our hypothesis that intravenously administered Pt-based chemotherapeutics are excreted into saliva and contribute to bitter taste dysfunctions via activation of oral TAS2Rs, and that HED shows a promising bitter-masking potential. To what extent the use of HED in cancer patients with bitter taste dysfunction may help to improve consecutive side effects such as loss of appetite, body weight and quality of life needs to be clarified in a clinical trial.

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