{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:43:20Z","timestamp":1792802600873,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Curcumin, a polyphenol isolated from the rhizome of\n                    <jats:italic>Curcuma longa<\/jats:italic>\n                    , has been studied because of its antioxidant, antimicrobial, and antiinflammatory properties. This study aimed to evaluate the effects of curcumin on head and neck cancer (HNC) cell lines and how it modulates the PI3K\u2013AKT\u2013mTOR signaling pathway. Dose\u2010response curves for curcumin were established for hypopharynx carcinoma (FaDu), tongue carcinoma (SCC\u20109), and keratinocytes (HaCaT) cell lines and IC\n                    <jats:sub>50<\/jats:sub>\n                    values were calculated. Cell cycle and cell death were investigated through flow cytometry. Cytoskeleton organization was assessed through phalloidin+FITC staining. qPCR array and western blot were performed to analyze gene and protein expression. Curcumin reduced cell viability in a dose\u2010dependent and selective manner, induced cell death on SCC\u20109 cells (necrosis\/late apoptosis: 44% curcumin vs. 16.4% vehicle), and arrested cell cycle at phase G\n                    <jats:sub>2<\/jats:sub>\n                    \/M on SCC\u20109 and FaDu (G\n                    <jats:sub>2<\/jats:sub>\n                    : SCC\u20109\u201419.1% curcumin vs. 13.4% vehicle; FaDu\u201437.8% curcumin vs. 12.9% vehicle). Disorganized cytoskeleton and altered cell morphology were observed. Furthermore, curcumin downregulated the PI3K\u2013AKT\u2013mTOR signaling pathway by modifying the expression of key genes and proteins. These findings highlight the promising therapeutic potential of curcumin to inhibit HNC growth and progression and to modulate the PI3K\u2013AKT\u2013mTOR pathway.\n                  <\/jats:p>","DOI":"10.1002\/ptr.6780","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T08:41:10Z","timestamp":1594024870000},"page":"3311-3324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Curcumin downregulates the\n                    <scp>PI3K\u2013AKT\u2013mTOR<\/scp>\n                    pathway and inhibits growth and progression in head and neck cancer cells"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-8782","authenticated-orcid":false,"given":"Gabriel Alvares","family":"Borges","sequence":"first","affiliation":[{"name":"Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology Oral Radiology and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"},{"name":"Laboratory of Oral Histopathology, Health Sciences Faculty University of Brasilia  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Taveira","family":"Elias","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Histopathology, Health Sciences Faculty University of Brasilia  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Amorim","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Histopathology, Health Sciences Faculty University of Brasilia  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Louren\u00e7o","family":"de Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Histopathology, Health Sciences Faculty University of Brasilia  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Della","family":"Coletta","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas  Piracicaba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio Moraes","family":"Castilho","sequence":"additional","affiliation":[{"name":"Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology Oral Radiology and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Helena","family":"Squarize","sequence":"additional","affiliation":[{"name":"Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology Oral Radiology and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-1550","authenticated-orcid":false,"given":"Eliete Neves Silva","family":"Guerra","sequence":"additional","affiliation":[{"name":"Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology Oral Radiology and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"},{"name":"Laboratory of Oral Histopathology, Health Sciences Faculty University of Brasilia  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6328"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12455"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.252"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1185399"},{"issue":"4","key":"e_1_2_7_8_1","first-page":"2895","article-title":"Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high\u2010risk or pre\u2010malignant lesions","volume":"21","author":"Cheng A. 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