Bitter taste receptors may hold potential as chemotherapeutic targets
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The body has 25 types of functional bitter taste receptors, but tasting is not their only function.
Research has shown these receptors also exist in the gastrointestinal tract and on the cells of extra-oral organs. Although the function of these receptors is not fully clear, they appear to prompt specific responses based on their location.
“Generally, bitter taste receptors are chemoreceptors, which means they respond to bitter stimuli. Therefore, if a bitter substance binds to the receptor, the receptor gets activated and triggers different responses depending on the cell type,” Agnes Mistlberger-Reiner, PhD, postdoctoral researcher in the department of physiological chemistry at University of Vienna, said in an interview with Healio. “In taste cells, where these receptors were first identified, the activation leads to the perception of bitter taste. Since it was thought that these receptors are specific for eliciting bitter taste, they were termed bitter taste receptors. Now it is clear that they can also have different functions.”
In addition, it appears that bitter taste receptors, also known as TAS2Rs, are present on cancer cells, making them potential therapeutic targets.
Mistlberger-Reiner was part of a team of researchers at University of Vienna, Leibniz Institute for Food Systems Biology at the Technical University of Munich, and Medical University of Vienna who conducted a systematic review study into the potential role of bitter taste receptors and cancer. She and her colleague, Sofie Zehentner, MSc, discussed their study and what it might mean for the future of cancer treatment.
Healio: Why do some extra-oral cells and organs have bitter taste receptors?
Zehentner: Since the discovery of bitter taste receptors on the cells of the tongue over 2 decades ago, TAS2Rs have been found in the gastrointestinal tract and many extra-oral tissues — including the airways, heart, thyroid, kidney, pancreas, skin, testis, uterus, breast and brain — as well as in blood and immune cells. The activation of these ectopically expressed TAS2Rs by bitter-tasting compounds has been associated with tissue-specific, functional responses. As the functional responses depend on the cell type activated, they are quite diverse. So far, just some nongustatory functionalities have been investigated, such as a stimulated proton secretion of gastric parietal cells, a secretion of satiating hormones, an involvement of TAS2Rs in anti-inflammatory processes, as well as an intra-cellular mobilization of calcium leading to the release of nitric oxide, and antimicrobial peptides in airway respiratory cells. Additionally, in recent years various effects on anticancer mechanisms were reported, which we reviewed in detail in our systematic review.
Healio: What is the purpose of bitter taste receptors on cancer cells?
Mistlberger-Reiner: This is not clear yet and needs further investigation. However, based on the studies we reviewed, we hypothesize that activation of bitter taste receptors elicits anticancer effects in diverse cells and leads to decreased cell growth, decreased migratory activity or cell death. Therefore, we further hypothesize that cancer cells downregulate bitter taste receptors to avoid these anticancer effects.
Healio: What was the goal of your study?
Mistlberger-Reiner: Funded by the Vienna Science and Technology Fund and supervised by Veronika Somoza, PhD, this study aimed to elucidate whether bitter taste receptors play a functional role in cancer development and to encourage more research toward this direction. Since a few rather old studies report alterations in taste perception in patients with cancer, it made us wonder whether taste receptors could have a function in cancer too. Bitter taste receptors are especially interesting in this regard, because many bitter-tasting compounds, such as plant extracts, showed anticancer activity. However, studies on the involvement of bitter taste receptors in these anticancer effects are very limited. Hence, we summarized the current state of research on this topic. With this systematic review, we hope to inspire other researchers to further explore this understudied area of cancer and its potential for cancer therapeutics.
Healio: How did you conduct your systematic review?
Mistlberger-Reiner: We analyzed the current state of research on the topic of bitter taste receptors and cancer using two electronic databases, GoogleScholar and PubMed, for our literature search. We included studies focusing on the current knowledge on the effects of genetic-mediated bitter taste perception on cancer risk. In addition, to gain a better understanding of the role of TAS2Rs in cancer, we included studies that examined the gene and protein expression of TASR2s, their agonist-mediated activation, the triggered effects at the cellular and molecular levels, and/or effects of survival time of patients. As the scientific literature about the role of bitter taste receptors in cancer is still an emerging field and only a very limited number of studies on this topic are available, we included all articles meeting the search strategy to provide a comprehensive overview on the current state of knowledge and encourage further research.
Healio: What did you find?
Zehentner: At first, we found evidence for down- and upregulations, although downregulations of various TAS2Rs were more prevalent. There are still some limitations, and the effects on cancer progression are poorly explored. Nevertheless, the detected differential expression levels of TAS2Rs underline their potential functional role in carcinogenesis. As highlighted in our systematic review, recent studies showed the activation of bitter taste receptors in cancer cells was predominantly associated with anticancer effects and the downregulation of some TAS2Rs was associated with poor prognosis, while overexpression counteracted cancer-promoting effects. These results support our hypothesis that TAS2Rs play a functional role in carcinogenesis and that their activation counteracts most typical capabilities of cancerous cells during cancer development and progression, known as hallmarks of cancer, such as avoiding growth suppression, deregulating cellular energetics and apoptosis, and promoting invasion and metastatic capabilities. Therefore, the downregulation of TAS2Rs could facilitate the avoidance of anticancer effects induced by the activation of TAS2Rs.
Healio: What are the potential implications of these findings for the future of cancer diagnosis and treatment?
Zehentner: Currently, we can only hypothesize because scientific data are limited, and more profound research is still needed. We suggest that specific bitter substances could be transported specifically to the tumor site to activate TAS2Rs of cancer cells and, thus, inhibit the tumor growth. Furthermore, if chemotherapeutic agents are proven to activate different TAS2Rs that lead to further anticancer effects via yet unknown mechanisms, they could be administered more specifically by adapting for the bitter taste receptors present in cancer tissues. It is possible that bitter receptors may be implicated in the treatment of different types of cancer in the future. However, a great deal of research is still needed.
For more information:
Agnes Mistlberger Reiner, PhD, can be reached at the University of Vienna, Faculty of Chemistry, Department of Physiological Chemistry, Josef-Holaubek-Platz 2/UZA II Room 2C584. A-1090, Vienna, Austria; email: agnes.mistlberger-reiner@univie.acat.
Sofie Zehentner, MsC, can be reached at the University of Vienna Faculty of Chemistry, Department of Physiological Chemistry, Josef-Holaubek-Platz 2/UZA II Room 2C584, A-1090, Vienna, Austria; email: sofie.zehentner@univie.ac.at.
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