Biology Reference
In-Depth Information
Chapter 3
Valerio Berardi, Francesca Ricci, Mauro Castelli, Gaspare Galati,
and Gianfranco Risuleo
INTRODUCTION
Resveratrol (RV) 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 demon-
strated, however at high concentrations the drug exhibits also an effective anti-prolif-
erative action. We recently showed its ability to abolish the effects of oxidative stress
in cultured cells. In this work we assayed the bioactivity of RV 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, RV
can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation
is that, due to the damage caused by RV 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.
The mouse fi broblast line 3T6 and the human tumor line HL60 were used through-
out 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.
Our results show a clear dose dependent both cytotoxic and antiviral effect of RV
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 ac-
tion is evident after the phase of virion entry, therefore data suggest that the drug acts
during the synthesis of the viral progeny DNA.
The RV 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 cytotoxicity may be attrib-
uted 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 RV make it a potential candidate for the clinical
control of proliferative as well as viral pathologies.
Murine polyomavirus (Py) is an ideal model system to investigate many differ-
ent biological phenomena at cellular and molecular level. Polyomavirus is totally
