title: Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.
abstract: Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L.) extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice) and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect.
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: González-Vallinas
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.affiliation: Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Vicente
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Zarza
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Martín-Hernández
authors.affiliation: Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Mónica R
authors.initials: MR
authors.lastname: García-Risco
authors.affiliation: Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fornari
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain; Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Reglero
authors.affiliation: Unit of Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute for Advanced Studies on Food (IMDEA-Food), Campus of International Excellence UAM+CSIC, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramírez de Molina
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D027542:Rosmarinus / Q000737:chemistry*
chemical_list: D004224:Diterpenes; D035683:MicroRNAs; D017351:N-Acetylglucosaminyltransferases; C117361:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3