PURPOSE: To determine the ability of @entity42840 to abrogate the cell cycle arrest induced by @entity9800 ( @entity1191 ) in @entity5 cells that lack @entity876 function, and therefore enhance the @entity137 of @entity1191 in these cells in relation to normal cells with wild-type @entity876 . METHODS: The responses of MDA-MB-231 and GI 101A @entity0 cells were compared to those of normal @entity291 endothelial cells. @entity137 was assessed by the @entity98 assay, and the resulting data were modeled using median-effect analysis. Inhibition of DNA synthesis was determined by loss of @entity665 incorporation, and cell cycle status was determined by flow cytometric analysis of @entity2667 -stained nuclei. RESULTS: @entity42840 , a specific inhibitor of protein kinase C (PKC) presently in clinical trials, abrogated @entity1191 -induced activation of S and G(2) checkpoints in @entity1 MDA-MB-231 and GI 101A @entity0 cells, both of which are mutants for the @entity876 gene. This abrogation occurred with the use of sublethal doses (100 nM) of @entity42840 and correlated with the enhancement of @entity1191 -induced @entity137 . Median-effect analysis showed that synergistic cytotoxic interactions existed between @entity1191 and @entity42840 against these @entity5 cells. In normal cells, however, abrogation of the S phase arrest caused accumulation in G(0)/G(1) phase, perhaps by the presence of wild-type @entity876 activity, with no change in @entity1191 -induced @entity137 . CONCLUSION: We have shown previously that the @entity137 of @entity1191 is correlated with cell cycle response in normal and @entity5 cells. Low doses of @entity1191 arrest cells in the G(2)/M phase and inhibit DNA synthesis, but higher doses cause arrest of cells in S phase. Thus modulation of events at the S and G(2) checkpoints may provide an opportunity to enhance @entity1191 -induced @entity137 in @entity5 cells. The results of this study indicate that @entity42840 enhances the progression of @entity5 cells through S phase thus greatly increasing @entity1191 -induced @entity137 . Normal cells, however, are able to arrest in G(0)/G(1) and thus avoid the increased @entity137 induced by @entity1191 . Our findings suggest potential usefulness of combining @entity42840 in topoisomerase I inhibitor-based drug therapy for the treatment of @entity0 with a dysfunctional @entity876 gene.

Enhancement of @entity9800 -induced @entity137 with XXXX in @entity0 cells: abrogation of S/G(2) arrest.

@entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'Cytotoxicity', 'cytotoxicity'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast carcinoma', 'breast cancer'] @entity2667 :: ('MESH:D011419', 'Chemical') :: ['propidium-iodide'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity665 :: ('CHEBI:53526', 'Chemical') :: ['[(3)H]thymidine'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity1191 :: ('CHEBI:27656', 'Chemical') :: ['CPT'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity9800 :: ('MESH:D002166', 'Chemical') :: ['camptothecin'] @entity291 :: ('9913', 'Species') :: ['bovine'] @entity42840 :: ('MESH:C054852', 'Chemical') :: ['UCN-01']
@entity42840 :: (MESH:C054852,Chemical) :: ['UCN-01']
