title: Shotgun proteomic analysis to study the decrease of xenograft tumor growth after rosemary extract treatment.
abstract: The antiproliferative activity of Rosemary (Rosmarinus officinalis) has been widely studied in different in vitro and in vivo models, which demonstrate that rosemary extracts inhibit the cellular proliferation due to its ability to interact with a wide spectrum of molecular targets. However, a comprehensive proteomics study in vivo has not been carried out yet. In the present work, the effects of rosemary extract on xenograft tumor growth has been studied and, for the first time, a shotgun proteomic analysis based on nano-LC-MS/MS together with stable isotope dimethyl labeling (DML) has been applied to investigate the global protein changes in vivo. Our results show that the daily administration of a polyphenol-enriched rosemary extract reduces the progression of colorectal cancer in vivo with the subsequent deregulation of 74 proteins. The bioinformatic analysis of these proteins indicates that the rosemary extract mainly alters the RNA Post-Transcriptional Modification, the Protein Synthesis and the Amino Acid Metabolism functions and suggests the inactivation of the oncogene MYC. These results demonstrate the high utility of the proposed analytical methodology to determine, simultaneously, the expression levels of a large number of protein biomarkers and to generate new hypothesis about the molecular mechanisms of this extract in vivo.
authors.affiliation: Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC), Nicolas Cabrera 9, 28049, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Valdés
authors.affiliation: Molecular Nutrition and Metabolism, Institute of Food Science Research (CIAL, CSIC), Nicolas Cabrera 9, 28049 Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: García-Cañas
authors.affiliation: Institute of Molecular and Cellular Biology, Miguel Hernández University, Avda. Universidad s/n, Elche 03202, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Pérez-Sánchez
authors.affiliation: Institute of Molecular and Cellular Biology, Miguel Hernández University, Avda. Universidad s/n, Elche 03202, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Barrajón-Catalán
authors.affiliation: Institute of Molecular and Cellular Biology, Miguel Hernández University, Avda. Universidad s/n, Elche 03202, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Ruiz-Torres
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Artemenko
authors.affiliation: Institute of Molecular and Cellular Biology, Miguel Hernández University, Avda. Universidad s/n, Elche 03202, Spain; CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC), Nicolas Cabrera 9, 28049, Madrid, Spain. Electronic address: a.cifuentes@csic.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cifuentes
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D040901:Proteomics / Q000379:methods*; D027542:Rosmarinus / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D010936:Plant Extracts; D059808:Polyphenols
keywords: Colon cancer; Dimethyl labeling; Mass spectrometry; Quantitative proteomics; Rosemary extract; Xenograft mice