title: Tamoxifen enhances the anti-proliferative effect of roscovitine, a selective cyclin-dependent kinase inhibitor, on human ER-positive human breast cancer cells.
abstract: We reported recently that roscovitine (ROSC), a selective cyclin-dependent kinase (CDK) inhibitor, can arrest human ER-positive MCF-7 breast cancer cells in the G2 phase of the cell cycle and concomitantly induce apoptosis. The observed effects of ROSC were diminished in MCF-7 cells maintained in the presence of estrogen-mimicking compounds. Therefore, we decided to test whether combining ROSC with anti-estrogen therapy would modulate the efficacy of ROSC action. Exposure of MCF-7 cells to tamoxifen (TAM) for 24 h decreased the number of living cells by approximately 10%. This was associated with a ca. 25% increase in the G1 cell population and reduction in the proportion of S-phase cells. Unlike TAM, estrogen had very weak effects on the cell cycle progression of MCF-7 cells within 24 h. The proliferation-promoting effect of estrogen did not become evident until cultivation of cells for 48 h. Addition of estrogen to MCF-7 cells 1 h prior to TAM administration abolished the anti-estrogen-induced G1 arrest. Simultaneous treatment of MCF-7 cells with ROSC and TAM strongly enhanced the anti-proliferative effect of ROSC. This was potentiated after co-treatment with estrogen. These results clearly indicate that the efficacy of treating ER-positive breast cancers by ROSC can be enhanced by combined application of antiestrogens.
authors.affiliation: Cell Cycle Regulation Group, Div., Institute of Cancer Research, Dept. of Medicine I, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Gritsch
authors.forename: Margarita
authors.initials: M
authors.lastname: Maurer
authors.forename: Nora
authors.initials: N
authors.lastname: Zulehner
authors.forename: Józefa
authors.initials: J
authors.lastname: Wesierska-Gadek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011687:Purines / Q000008:administration & dosage; D000077546:Roscovitine; D016196:S Phase / Q000187:drug effects*; D013629:Tamoxifen / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D011687:Purines; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases