Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use.
BACKGROUND
Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA.


METHODS
The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols.


RESULTS
Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6) as well as a tumor-line (HL60). Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA.


CONCLUSIONS
Resveratrol is cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies.
Berardi
Valerio
V
Dipartimento di Genetica e Biologia Molecolare, Sapienza Università di Roma, Roma, Italy. valerio.berardi@uniroma1.it
Ricci
Francesca
F
Castelli
Mauro
M
Galati
Gaspare
G
Risuleo
Gianfranco
G
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D011120:Polyomavirus / Q000187:drug effects* / Q000235:genetics; D027601:Polyomavirus Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
D016588:Anticarcinogenic Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D013267:Stilbenes; D000077185:Resveratrol