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- W3207900853 abstract "2663 The oncogenic transcription factor forkhead box M1 (FoxM1) is overexpressed in a number of different carcinomas, whereas its expression is turned off in terminally differentiated cells. For this reason, FoxM1 is an attractive target for therapeutic intervention in cancer treatment. As a first step toward realizing this goal, in this study, using a high-throughput, cell based assay system, we screened for and isolated the antibiotic thiazole compound Siomycin A as an inhibitor of FoxM1 transcriptional activity. Interestingly, we observed that Siomycin A was able to down-regulate the transcriptional activity as well as the protein and mRNA levels of FoxM1. Consequently, we found that the downstream target genes of FoxM1, such as Cdc25B, Survivin, and CENPB, were also repressed. However, thiazole antibiotics did not affect transcriptional activity of p53, TCF/Lef or GLI suggesting that they specifically target FoxM1. Furthermore, we found that thiazole antibiotics were able inhibit the growth of human cancer cells of different origin with IC50 between 0.5 and 5 I¼M. Siomycin A induced apoptosis selectively in transformed, but not in normal human fibroblasts. Treatment of human cancer cell lines of different origin with 1-5 I¼M of thiazole antibiotics led to predominant down-regulation of FoxM1 and apoptosis. Taken together, our data suggest that thiazole antibiotics that inhibit FoxM1 could represent a useful starting point for the development of anticancer therapeutics against human neoplasia." @default.
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- W3207900853 date "2008-05-01" @default.
- W3207900853 modified "2023-09-28" @default.
- W3207900853 title "Thiazole antibiotics that inhibit FoxM1 are potential anticancer drugs" @default.
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