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At present, the anti\u2010tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u20108, <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B, <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201038 and <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20103. Among the cells tested, meridianin C most strongly reduced the growth of <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B cells; confirmed by the microscopic and <jats:styled-content style=\"fixed-case\">TEM<\/jats:styled-content> analysis as well as the entry of <jats:styled-content style=\"fixed-case\">FITC<\/jats:styled-content>\u2010dextran, which was sensitive to the macropinocytosis inhibitor amiloride. <jats:styled-content style=\"fixed-case\">SEM<\/jats:styled-content> data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B cells treated with meridianin C, pointing out that meridianin C\u2010induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf\u2010related protein\u20103 (<jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>\u20103), a known negative regulator of macropinocytosis. A role for <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>\u20103 in regulating macropinocytosis in the <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B cells was confirmed by si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> knockdown of endogenous <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>\u20103, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>\u20103 overexpression, which resulted in a considerable inhibition of the meridianin C\u2010induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti\u2010proliferative effects via macropinocytosis in the highly tumorigenic <jats:styled-content style=\"fixed-case\">YD<\/jats:styled-content>\u201010B cell line and the effects are mediated in part through down\u2010regulation of <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>\u20103.<\/jats:p>","DOI":"10.1111\/jcmm.13854","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T07:50:08Z","timestamp":1537775408000},"page":"5833-5846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Meridianin C inhibits the growth of YD\u201010B human tongue cancer cells through macropinocytosis and the down\u2010regulation of Dickkopf\u2010related protein\u20103"],"prefix":"10.1111","volume":"22","author":[{"given":"Nam\u2010Sook","family":"Park","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine College of Medicine Keimyung University Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Kyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine College of Medicine Keimyung University Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Ramalingam","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine College of Medicine Keimyung University Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine College of Medicine Keimyung University Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo\u2010Rim","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine College of Medicine 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