{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:40:47Z","timestamp":1782409247583,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T00:00:00Z","timestamp":1398643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000690","name":"Research Councils UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SWan SouthWest Academic Network","award":["CarewBainesWilliams"],"award-info":[{"award-number":["CarewBainesWilliams"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Identifying and characterizing potential new therapeutic agents to target cell proliferation may provide improved treatments for neoplastic disorders such as cancer and polycystic diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used the simple, tractable biomedical model <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ictyostelium<\/jats:italic> to investigate the molecular mechanism of naringenin, a dietary flavonoid with antiproliferative and chemopreventive actions <jats:italic>in vitro<\/jats:italic> and in animal models of carcinogenesis. We then translated these results to a mammalian kidney model, <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>adin\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>arby canine kidney (<jats:styled-content style=\"fixed-case\">MDCK<\/jats:styled-content>) tubule cells, grown in culture and as cysts in a collagen matrix.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Naringenin inhibited <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ictyostelium<\/jats:italic> growth, but not development. Screening of a library of random gene knockout mutants identified a mutant lacking TRPP2 (polycystin\u20102) that was resistant to the effect of naringenin on growth and random cell movement. <jats:styled-content style=\"fixed-case\">TRPP2<\/jats:styled-content> is a divalent transient receptor potential cation channel, where mutations in the protein give rise to type 2 autosomal dominant polycystic kidney disease (<jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>). Naringenin inhibited <jats:styled-content style=\"fixed-case\">MDCK<\/jats:styled-content> cell growth and inhibited cyst growth. Knockdown of TRPP2 levels by <jats:styled-content style=\"fixed-case\">siRNA<\/jats:styled-content> in this model conferred partial resistance to naringenin such that cysts treated with 3 and 10\u2009\u03bcM naringenin were larger following TRPP2 knockdown compared with controls. Naringenin did not affect chloride secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The action of naringenin on cell growth in the phylogenetically diverse systems of <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ictyostelium<\/jats:italic> and mammalian kidney cells, suggests a conserved effect mediated by <jats:styled-content style=\"fixed-case\">TRPP2<\/jats:styled-content> (polycystin\u20102). Further studies will investigate naringenin as a potential new therapeutic agent in <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue-10\">http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue\u201010<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12443","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:57:38Z","timestamp":1381543058000},"page":"2659-2670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Naringenin inhibits the growth of <i><scp>D<\/scp>ictyostelium<\/i> and <scp>MDCK<\/scp>\u2010derived cysts in a <scp>TRPP2<\/scp> (polycystin\u20102)\u2010dependent manner"],"prefix":"10.1111","volume":"171","author":[{"given":"A","family":"Waheed","sequence":"first","affiliation":[{"name":"School of Pharmacy &amp; Chemistry Kingston University  Kingston upon Thames Surrey 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