Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 11; p. 1940
• Main Authors: Nivelle, Laetitia, Hubert, Jane, Courot, Eric, Borie, Nicolas, Renault, Jean-Hugues, Nuzillard, Jean-Marc, Harakat, Dominique, Clément, Christophe, Martiny, Laurent, Delmas, Dominique, Jeandet, Philippe, Tarpin, Michel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-11-2017; MDPI
• Subjects: Acetic acid; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Biochemistry, Molecular Biology; Biological activity; bioreactor; Bioreactors; Biotechnology; Cancer; Cell Line, Tumor; Cell Survival - drug effects; Cell suspensions; Communication; cytotoxic activity; Cytotoxicity; Dimerization; Ethyl acetate; fibroblasts; Humans; Inhibition; Ionization; labruscol; Life Sciences; Magnetic Resonance Spectroscopy; Mass spectrometry; Mass spectroscopy; Melanoma; Melanoma, Cutaneous Malignant; Molecular biology; Molecular Structure; NMR; Nuclear magnetic resonance; Plant Cells; Resveratrol; Skin; Skin cancer; Skin Neoplasms; Spectroscopy; Stereochemistry; Stilbene; Stilbenes - chemistry; Stilbenes - isolation & purification; Stilbenes - pharmacology; Tumor cell lines; Two dimensional analysis; Vitis; Vitis labrusca L; fibroblasts; melanoma; cytotoxic activity; bioreactor; resveratrol; Vitis labrusca L; labruscol
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22111940

A new resveratrol dimer (
) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of
L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) analyses including ¹H,
C, 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.