{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:27:41Z","timestamp":1791304061629,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4\u2010nitro quinoline\u20101\u2010oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)\u2010driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC\u2010specific markers (\n                      <jats:italic>CD44<\/jats:italic>\n                      and\n                      <jats:italic>CD133<\/jats:italic>\n                      ) was observed from 8th to 25th week, at transcript (40\u2010100\u2010fold) and protein levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009\u2264\u20090.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4\u2009mm\n                      <jats:sup>3<\/jats:sup>\n                      ;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04) and improved overall survival of the animals (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO\u2010induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). The treatment also inhibited the migratory and self\u2010renewal properties of these cells; the effect of which was prominent in the cultures of early dysplastic tissue (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.002). Collectively, our observations suggest that the combination of curcumin and metformin may improve chemopreventive efficacy against oral squamous cell carcinoma through a CSC\u2010associated mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22692","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T17:27:48Z","timestamp":1497547668000},"page":"2446-2460","source":"Crossref","is-referenced-by-count":61,"title":["Curcumin and metformin\u2010mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells"],"prefix":"10.1002","volume":"56","author":[{"given":"Gangotri","family":"Siddappa","sequence":"first","affiliation":[{"name":"Integrated Head and Neck Oncology Research Program, DSRG\u20105 Mazumdar Shaw Centre for Translational Research Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"},{"name":"Head and Neck Oncology Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safeena","family":"Kulsum","sequence":"additional","affiliation":[{"name":"Integrated Head and Neck Oncology Research Program, DSRG\u20105 Mazumdar Shaw Centre for Translational Research Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"},{"name":"School of Biosciences and Technology VIT University Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doddathimmasandra Ramanjanappa","family":"Ravindra","sequence":"additional","affiliation":[{"name":"Integrated Head and Neck Oncology Research Program, DSRG\u20105 Mazumdar Shaw Centre for Translational Research Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay V.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Dr. BR Ambedkar Medical College Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalini","family":"Raju","sequence":"additional","affiliation":[{"name":"Department of Histopathology Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisheena","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Histopathology Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holalugunda Vittalamurthy","family":"Sudheendra","sequence":"additional","affiliation":[{"name":"Integrated Head and Neck Oncology Research Program, DSRG\u20105 Mazumdar Shaw Centre for Translational Research Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Sharma","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory GROW Laboratory Narayana Nethralaya Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumsum P.","family":"Sunny","sequence":"additional","affiliation":[{"name":"Integrated Head and Neck Oncology Research Program, DSRG\u20105 Mazumdar Shaw Centre for Translational Research Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"},{"name":"Head and Neck Oncology Mazumdar Shaw Medical Centre Narayana Health Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Microbiology Bangalore Institute of Dental Sciences Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binu T.","family":"Kuruvilla","sequence":"additional","affiliation":[{"name":"Arjuna Natural Extracts Ltd. 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