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Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2 (polycystin-2)-dependent manner.

Waheed, A; Ludtmann, MH; Pakes, N; Robery, S; Kuspa, A; Dinh, C; Baines, D; Williams, RS; Carew, MA (2014) Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2 (polycystin-2)-dependent manner. British Journal of Pharmacology, 171 (10). pp. 2659-2670. ISSN 1476-5381 https://doi.org/10.1111/bph.12443
SGUL Authors: Baines, Deborah

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Abstract

BACKGROUND AND PURPOSE: Identifying and characterizing potential new therapeutic agents to target cell proliferation may provide improved treatments for neoplastic disorders such as cancer and polycystic diseases. EXPERIMENTAL APPROACH: We used the simple, tractable biomedical model Dictyostelium to investigate the molecular mechanism of naringenin, a dietary flavonoid with antiproliferative and chemopreventive actions in vitro and in animal models of carcinogenesis. We then translated these results to a mammalian kidney model, Madin-Darby canine kidney (MDCK) tubule cells, grown in culture and as cysts in a collagen matrix. KEY RESULTS: Naringenin inhibited Dictyostelium growth, but not development. Screening of a library of random gene knockout mutants identified a mutant lacking TRPP2 (polycystin-2) that was resistant to the effect of naringenin on growth and random cell movement. TRPP2 is a divalent transient receptor potential cation channel, where mutations in the protein give rise to type 2 autosomal dominant polycystic kidney disease (ADPKD). Naringenin inhibited MDCK cell growth and inhibited cyst growth. Knockdown of TRPP2 levels by siRNA in this model conferred partial resistance to naringenin such that cysts treated with 3 and 10 μM naringenin were larger following TRPP2 knockdown compared with controls. Naringenin did not affect chloride secretion. CONCLUSIONS AND IMPLICATIONS: The action of naringenin on cell growth in the phylogenetically diverse systems of Dictyostelium and mammalian kidney cells, suggests a conserved effect mediated by TRPP2 (polycystin-2). Further studies will investigate naringenin as a potential new therapeutic agent in ADPKD.

Item Type: Article
Additional Information: © 2013 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Dictyostelium, cell growth, naringenin, polycystic kidney disease, polycystin-2, polyphenol, Animals, Antiprotozoal Agents, Cell Proliferation, Dose-Response Relationship, Drug, Dogs, Flavanones, Kidney, Madin Darby Canine Kidney Cells, Mutation, Polycystic Kidney, Autosomal Dominant, Protozoan Proteins, RNA Interference, TRPP Cation Channels, Time Factors, Transfection, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, POLYCYSTIC KIDNEY-DISEASE, ENZYME-MEDIATED INTEGRATION, CELL-PROLIFERATION, CHLORIDE SECRETION, DISCOIDEUM AMEBAS, CFTR INHIBITORS, CATION CHANNEL, VALPROIC ACID, FLAVONOIDS, MOTILITY, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: British Journal of Pharmacology
ISSN: 1476-5381
Language: eng
Dates:
DateEvent
May 2014Published
PubMed ID: 24116661
Web of Science ID: WOS:000334973100014
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107298
Publisher's version: https://doi.org/10.1111/bph.12443

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