Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.

Laetitia Nivelle (1) , Jane Hubert (2) , Eric Courot (3) , Philippe Jeandet (3) , Aziz Aziz (3) , Jean-Marc Nuzillard (2) , Jean-Hugues Renault (2) , Christophe Clément (3) , Laurent Martiny (1) , Dominique Delmas (4) , Michel Tarpin (1)

1 MEDyC - Matrice Extracellulaire et Dynamique Cellulaire - UMR CNRS 7369
2 ICMR - Institut de Chimie Moléculaire de Reims - UMR 7312
3 URVVC - Unité de Recherche Vigne et Vins de Champagne Stress et Environnement - EA 4707
4 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]

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 (13)C-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.

Mots clés: Vitis labrusca; phytostilbenes; melanoma; resveratrol; anticancer activity; bioreactor; fibroblasts

Domaines: Chimie organique; Biochimie, Biologie Moléculaire

Laetitia Nivelle, Jane Hubert, Eric Courot, Philippe Jeandet, Aziz Aziz, et al.. Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.. Molecules, 2017, 22 (3), pp.474. ⟨10.3390/molecules22030474⟩. ⟨hal-01555716⟩