Antiproliferative activities of resveratrol and related compounds in human hepatocyte derived HepG2 cells are associated with biochemical cell disturbance revealed by fluorescence analyses.

Date publication

novembre 2008

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DELMAS Dominique , Dr LANCON Allan

Tous les auteurs :
Colin D, Lancon A, Delmas D, Lizard G, Abrossinow J, Kahn E, Jannin B, Latruffe N

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/18627786

Résumé

Resveratrol is a well known polyphenol largely produced in grapevine. It is a strong antioxidant and a free radical scavenger. It exhibits several beneficial effects for health including cancer. Resveratrol antioxidant activity is essential in the prevention of chemical-induced cancer by inhibiting initiation step of carcinogenesis process but it is also considered to inhibit cancer promotion and progression steps. While the effects of resveratrol on cancer cells are widely described, the data available on the antiproliferative potential of resveratrol derivatives remain weak. Nevertheless, resveratrol analogs could exhibit stronger potentials than the parent molecule. So, we compared the cellular effects of trans-resveratrol, trans-epsilon-viniferin and their respective acetate derivatives, as well as a polyphenol mixture extracted from grapevine shoots, called vineatrol. We studied their abilities to interfere with cell proliferation, their uptake and their effects on parameters of cellular state in human hepatoma cells (HepG2). Cell growth experiments show that resveratrol triacetate presents a slightly better antiproliferative potential than resveratrol. The dimer epsilon-viniferin,as well as its pentaacetate analog, is less powerful than resveratrol, although a similar uptake kinetics in cells. Interestingly, among the tested polyphenols, vineatrol is the most potent solution, indicating a possible synergistic effect of both resveratrol and epsilon-viniferin. We took advantage of the fluorescence properties of these compounds to evidence cellular uptake by using flow cytometry. In addition, by competition assay, we demonstrate that resveratrol triacetate enters in hepatic HepG2 cells by the same way as resveratrol. By autofluorescence in situ measurement we observed that resveratrol and related compounds induce deep changes in cells activity. These changes occur mainly by increasing NADPH cell content and the number of green fluorescent cytoplasmic granular structures which may be related to an induction of detoxifying enzyme mechanisms.

Référence

Biochimie. 2008 Nov-Dec;90(11-12):1674-84