Effects Of Resveratrol On Cell Cycle Regulatory Processes Of Mice Fibrosarcoma S180 Cells And Their Mechanisms

Objective:The morbility and mortality of malignant tumors have been showing a tendency to increase in recent years.Cancer has become the first cause of death in urban and rural areas in our country.Presently, surgery,chemotherapy,radiotherapy and biotherapy are the main therapeutic methods.The traditional chemotherapeutics are restricted to tumor patients because of their heavy side reactions and multidrug resistances.These drugs also kill the nomal cells.The attractiveness of naturally occurring compounds for cancer chemoprevention has escalated in recent years.Resveratrol has been shown to be an effective chemopreventive agent in multiple murine models of human cancers.It has the capacity to interact with multiple molecular targets and appears to be relatively non-toxic at least at the doses tested in these models.But there are few researchs about resveratrol inhibits fibrosarcoma tumor growth.The aim of this study was to investigate the anticancer activities of resveratrol on mice fibrosarcoma S180 cells and their molecular mechanisms involved.To study the effect of resveratrol on the expression of cyclinD1 and P21^Cip1protein in the cell cycle.Methods:(1)The effects of resveratrol on the growth of mice fibrosarcoma cell lines S180 were studied by MTT assay.(2)The effect of resveratrol on the cell cycle phase distribution of S180 cells were analyzed using flow cytometry by a propidium iodide method.(3)The effect of resveratrol on the expression of cyclinD1 and P21^Cip1protein was studied by Western blot analysis.Results:(1)Resveratrol had a dual effect on the growth of S180 cells:At low concentrations,it increased the growth of S180 cells,and at high concentrations,it inhibited the proliferation of S180 cells in a time and dose dependent manner.(2)Flow cytometric analyses showed that S180 cells treated with resveratrol were accumulated in G₀/G₁ phase in the cell cycle,the ratio of cells in G₂/M phase was decreased at 24 h treatment.(3)The expression of cyclinD1 protein was decreased in a time dependent manner in S180 cells treated with resveratrol,while P21^Cip1 protein was increased.Conclusion:(1)Our studies demonstrate a biphasic,dual effect of resveratrol that play an important role in determining cell viability.(2) Resveratrol is able to inhibit the proliferation of S180 cells by regulating the cell cycle at high concentrations.Regulating the expression of cell cycle regulatory protein may suggest an involvement in the resveratrol-induced cell cycle arrest.(3)We suggest the series of events by which resveratrol results in an imposition of an artificial checkpoint at G₁-S phase transition,thereby resulting in an arrest of cancer cells in the G₁ phase of the cell cycle.(4)Resveratrol,a naturally occurring compounds,is a promising,novel therapeutic agent for cancer prevention and therapy.