title: Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.
abstract: In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a13C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4'), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC50values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.
authors.affiliation: Unité Matrice Extracellulaire et Dynamique Cellulaire, UMR CNRS 7369, SFR Cap-Santé FED 4231, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. laetitia.nivelle@univ-reims.fr.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Nivelle
authors.affiliation: Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, SFR Cap-Santé FED 4231, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51687 Reims CEDEX 2, France. laurent.martiny@univ-reims.fr.
authors.forename: Jane
authors.initials: J
authors.lastname: Hubert
authors.affiliation: Unité de Recherche Vignes et Vins de Champagne EA 4707, SFR Condorcet FR CNRS 3417, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. eric.courot@univ-reims.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Courot
authors.affiliation: Unité de Recherche Vignes et Vins de Champagne EA 4707, SFR Condorcet FR CNRS 3417, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. philippe.jeandet@univ-reims.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jeandet
authors.affiliation: Unité de Recherche Vignes et Vins de Champagne EA 4707, SFR Condorcet FR CNRS 3417, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. michel.tarpin@univ-reims.fr.
authors.forename: Aziz
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, SFR Cap-Santé FED 4231, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51687 Reims CEDEX 2, France. jane.hubert@univ-reims.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nuzillard
authors.affiliation: Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, SFR Cap-Santé FED 4231, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51687 Reims CEDEX 2, France. jean-marc.nuzillard@univ-reims.fr.
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Renault
authors.affiliation: Unité de Recherche Vignes et Vins de Champagne EA 4707, SFR Condorcet FR CNRS 3417, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. jh.renault@univ-reims.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Clément
authors.affiliation: Unité Matrice Extracellulaire et Dynamique Cellulaire, UMR CNRS 7369, SFR Cap-Santé FED 4231, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. aziz.aziz@univ-reims.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martiny
authors.affiliation: Centre de Recherche Inserm U866, Université de Bourgogne, 21000 Dijon, France. christophe.clement@univ-reims.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Delmas
authors.affiliation: Unité Matrice Extracellulaire et Dynamique Cellulaire, UMR CNRS 7369, SFR Cap-Santé FED 4231, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France. dominique.delmas@u-bourgogne.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Tarpin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis* / Q000494:pharmacology*; D061249:Batch Cell Culture Techniques; D019149:Bioreactors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D059828:Plant Cells / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D027843:Vitis / Q000166:cytology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D000077185:Resveratrol
keywords: Vitis labrusca; anticancer activity; bioreactor; fibroblasts; melanoma; phytostilbenes; resveratrol