Gut tumors in flies alter the taste valence of an anti-tumorigenic bitter compound

TitleGut tumors in flies alter the taste valence of an anti-tumorigenic bitter compound
Publication TypeJournal Article
Year of Publication2024
AuthorsLeung NY *, Xu C*, Li JShing Shun, Ganguly A*, Meyerhof GT *, Regimbald-Dumas Y, Lane EA, Breault DT, He X, Perrimon N, Montell C
JournalCurr Biol
Volume34
Issue12
Pagination2623-2632.e5
Date Published2024 Jun 17
ISSN1879-0445
KeywordsAnimals, Aristolochic Acids, Drosophila melanogaster, Intestinal Neoplasms, Taste
Abstract

The sense of taste is essential for survival, as it allows animals to distinguish between foods that are nutritious from those that are toxic. However, innate responses to different tastants can be modulated or even reversed under pathological conditions. Here, we examined whether and how the internal status of an animal impacts taste valence by using Drosophila models of hyperproliferation in the gut. In all three models where we expressed proliferation-inducing transgenes in intestinal stem cells (ISCs), hyperproliferation of ISCs caused a tumor-like phenotype in the gut. While tumor-bearing flies had no deficiency in overall food intake, strikingly, they exhibited an increased gustatory preference for aristolochic acid (ARI), which is a bitter and normally aversive plant-derived chemical. ARI had anti-tumor effects in all three of our gut hyperproliferation models. For other aversive chemicals we tested that are bitter but do not have anti-tumor effects, gut tumors did not affect avoidance behaviors. We demonstrated that bitter-sensing gustatory receptor neurons (GRNs) in tumor-bearing flies respond normally to ARI. Therefore, the internal pathology of gut hyperproliferation affects neural circuits that determine taste valence postsynaptic to GRNs rather than altering taste identity by GRNs. Overall, our data suggest that increased consumption of ARI may represent an attempt at self-medication. Finally, although ARI's potential use as a chemotherapeutic agent is limited by its known toxicity in the liver and kidney, our findings suggest that tumor-bearing flies might be a useful animal model to screen for novel anti-tumor drugs.

DOI10.1016/j.cub.2024.04.082
Alternate JournalCurr Biol
PubMed ID38823383
PubMed Central IDPMC11308992
Grant ListF31 EY027191 / EY / NEI NIH HHS / United States
F32 MH125593 / MH / NIMH NIH HHS / United States
R01 DC016278 / DC / NIDCD NIH HHS / United States
R01 DK121945 / DK / NIDDK NIH HHS / United States
R01 GM126120 / GM / NIGMS NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
R01 DC007864 / DC / NIDCD NIH HHS / United States
R35 GM134953 / GM / NIGMS NIH HHS / United States
R01 GM067761 / GM / NIGMS NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
P30 DK034854 / DK / NIDDK NIH HHS / United States