Roscovitine inhibits the proliferative activity of immortal and neoplastic human breast epithelial cells.
[2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylp urine] (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases cdc2 and cdk2. In this study, we evaluated the potential involvement of this novel cyclin-dependent kinase inhibitor in the proliferative activity of malignant and non-malignant human breast epithelial cells in vitro. Estrogen receptor-positive MCF-7 breast carcinoma cells, immortalized estrogen receptor-negative breast epithelial cells and highly malignant estrogen receptor-negative MDA-MB-231 breast epithelial cells, were incubated with different concentrations of roscovitine ranging from 1 to 40 micrograms/ml, and cell numbers were measured with the WST-1 colorimetric assay after 24, 48, 72, 96, 120, and 144 hours of treatment. Our results demonstrated that roscovitine inhibited the proliferation of human breast epithelial cells in a dose- and time-dependent manner. Roscovitine treatment decreased the number of viable cells and prevented the exponential growth of all the cell lines examined. The antiproliferative 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.
Mgbonyebi
O P
OP
Breast Cancer Research Laboratory, Fox Chase Cancer Center Philadelphia, PA 19111, USA.
Russo
J
J
Russo
I H
IH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011687:Purines / Q000494:pharmacology*; D000077546:Roscovitine; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases