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- W2999470382 abstract "2137 Objective: To evaluate the potential synergistic effect of the combination compared to single drug treatment using Manumycin A (MA) and Mebendazole (Mbz). And to determine the significance of sequential over concurrent treatment using these two drugs. Methods: Three breast cancer cell-lines (MDA-MB-231, MCF-7 and MCF-7 Her-18) were grown in DMEM medium in 96-well microplates (at 5,000 cells in 100 μL culture medium). Drug stock solutions were separately prepared in sterile DMSO, and further diluted with 0.1% DMSO containing culture medium to achieve the IC25 concentrations of MA and Mbz previously determined for each cell-line. For concurrent treatment, MA was combined with Mbz and incubated at 37oC for 48 hours. For sequential treatments, either MA or Mbz was incubated at 37oC for 24 hours, then the cells were washed with PBS, MA treated cells received Mbz, while the Mbz treated cells received MA. Microplates were incubated for an additional 24 hours. Cell viability was determined using XTT assay, n= 16 for each treatment from 2-3 independent runs. Results: For treatment with MA as a single agent the percent viabilities (%+SD) were 63.3+10.7 for MDA-MB-231, 65.7+3.4 for MCF-7, and 67.9+ 10.2 for MCF-7 Her-18. Percent viabilities for Mbz as a single agent were 91.9+16.5, 76.7+3.7, and 93.3+6.2 for MDA-MB-231, MCF-7, and MCF-7 Her-18, respectively. For concurrent treatment the percent viabilities (%+SD) were 60.0+7.6 for MDA-MB-231, 54.5+4.2 for MCF-7, and 61.1+ 26.0 for MCF-7 Her-18. The concurrent treatment did not enhance the effect of MA using a single agent, except in MCF-7 that the percent viability further decreased from 65.7 to 54.5%. For sequential treatment with MA first the percent viabilities were: 49.9+9.8, 27.0+4.8, and 20.0+ 9.6 for MDA-MB-231, MCF-7, and MCF-7 Her-18 respectively. While the percent viabilities with Mbz-first treatment were: 48.3+28, 47.45+8.26, and 32.12+ 9.53 for MDA-MB-231, MCF-7, and MCF-7 Her-18 respectively. Sequential treatments significantly enhanced the cytotoxicity of individual agents. In all three cell lines, sequential treatments with the two protocols exerted enhancements. The MA-first sequence was more effective than Mbz-first. Greater enhancements were observed in MCF-7 and MCF-7 Her-18 than in MB-231for MA-first sequential treatment. The MCF-7 Her-18 is more susceptible than the other two lines when Mbz was used first. Conclusion: In all three cell lines, Sequential treatment was superior to concurrent treatment. MA first treatment was more effective compared to Mbz first in MCF-7 and MCF-7 Her18 cells. While the sequence did not have an effect in MDA-231 cells." @default.
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- W2999470382 date "2006-04-15" @default.
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- W2999470382 title "Sequential versus concurrent treatment of breast cancer cell-lines using the farnesyl transferase inhibitor, manumycin A, and mebendazole" @default.
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