Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor
Laetitia Nivelle,
Jane Hubert,
Eric Courot,
Philippe Jeandet,
Aziz Aziz,
Jean-Marc Nuzillard,
Jean-Hugues Renault,
Christophe Clément,
Laurent Martiny,
Dominique Delmas,
Michel Tarpin
Affiliations
Laetitia Nivelle
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
Jane Hubert
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
Eric Courot
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
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
Aziz Aziz
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
Jean-Marc Nuzillard
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-Hugues Renault
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
Christophe Clément
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
Laurent Martiny
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
Centre de Recherche Inserm U866, Université de Bourgogne, 21000 Dijon, France
Michel Tarpin
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
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 a 13C-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 IC50 values 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.
