Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144
Laetitia Nivelle,
Jane Hubert,
Eric Courot,
Nicolas Borie,
Jean-Hugues Renault,
Jean-Marc Nuzillard,
Dominique Harakat,
Christophe Clément,
Laurent Martiny,
Dominique Delmas,
Philippe Jeandet,
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
Nicolas Borie
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
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
Dominique Harakat
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
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
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
A new resveratrol dimer (1) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of Vitis labrusca L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) analyses including 1H, 13C, heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and correlation spectroscopy (COSY) as well as high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) were used to characterize this compound and to unambiguously identify it as a new stilbene dimer, though its relative stereochemistry remained unsolved. Labruscol was recovered as a pure compound (>93%) in sufficient amounts (41 mg) to allow assessment of its biological activity (cell viability, cell invasion and apoptotic activity) on two different cell lines, including one human skin melanoma cancer cell line HT-144 and a healthy human dermal fibroblast (HDF) line. This compound induced almost 100% of cell viability inhibition in the cancer line at a dose of 100 μM within 72 h of treatment. However, at all tested concentrations and treatment times, resveratrol displayed an inhibition of the cancer line viability higher than that of labruscol in the presence of fetal bovine serum. Both compounds also showed differential activities on healthy and cancer cell lines. Finally, labruscol at a concentration of 1.2 μM was shown to reduce cell invasion by 40%, although no similar activity was observed with resveratrol. The cytotoxic activity of this newly-identified dimer is discussed.
