ROSCOVITINE INHIBITS THE PROLIFERATIVE ACTIVITY OF IMMORTAL AND NEOPLASTIC HUMAN BREAST EPITHELIAL-CELLS

ydroxyethylamino)-6-benzylamino-9-isopropylpurine] (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases cdc2 and cd k2. In this study: we evaluated the potential involvement of this nove l cyclin-dependent kinase inhibitor in the proliferative activity of m alignant and non-malignant human breast epithelial cells in vitro. Est rogen receptor positive MCF-7 breast carcinoma cells, immortalized est rogen receptor negative breast epithelial cells and highly malignant e strogen receptor-negative MDA-MB-231 breast epithelial cells, were inc ubated with different concentrations of roscovitine ranging from 1 to 40 mu g/ml, and cell numbers were measured with the WST-1 colorimetric assay after 24, 48, 72, 96, 120, and 144 hours of treatment. Our resu lts demonstrated that roscovitine inhibited the proliferation of human breast epithelial cells in a dose- and time-dependent manner. Roscovi tine treatment decreased the number of viable cells and prevented the exponential growth of all the cell lines examined. The antiproliferati ve effect of this potent cdk inhibitor was independent of the estrogen receptor status of the cells. These data suggest that roscovitine is a potential antiproliferative drug for the treatment and/or prevention of both estrogen responsive and non-responsive breast cancers.