Ursolic acid mediated inhibition of human prostate cancer cell growth in vitro involves alterations in cell cycle related protein expression

Ursolic acid is a constituent of the American cranberry (Vaccinium macrocarpon) and other Vaccinium fruit found primarily in the peel. In this study, the effects of ursolic acid (UA) on the cell cycle behaviour of DU145 human prostate cancer cells in vitro was examined. Following treatment of cells with UA (50 μM) for 6 hours, the cellular viability of the cells decreased. UA treatment increased the proportion of cells in the G1 phase of the cell cycle. The relative proportion of cells in G2-M phase was similar in both control and UA-treated cells. UA treatment also caused a decrease in the proportion of cells in S-phase relative to untreated cells. These cell cycle alterations were associated with changes in expression of cell cycle associated regulatory proteins. UA decreased the protein expression levels of cyclin A, cyclin D, p16 , pRBp107 and increased the expression of CDK2, CDK4, cyclin E, p21, p27 and pRBp130. CyclinB1 protein expression levels were apparently unaffected by UA. These findings demonstrate that ursolic acid can affect the cell growth behaviour of human prostate cancer cells in vitro. [Cranberry Institute (Wisconsin Board) & Telus MRFD Prostate Cancer Research Fund (PEI Division) funded]