BACKGROUND: The oncogenic transcription factor forkhead box M1 (FoxM1) is upregulated in a wide range of different carcinomas, while its expression is turned off in terminally differentiated cells. In addition, FoxM1 is involved in tumor invasion, angiogenesis and metastasis. For these reasons, FoxM1 is an appealing target for anticancer therapeutics. OBJECTIVE/ METHODS: In the quest to develop novel anticancer drugs we decided to target oncogenic transcription factor FoxM1 in tumor cells. Using a cell-based screening system we isolated the thiazole antibiotic siomycin A as inhibitor of FoxM1 transcriptional activity. In addition, we found that because of FoxM1 positive-autoregulation loop siomycin A and another thiazole antibiotic thiostrepton inhibit not only FoxM1 transcriptional activity but also its expression. However, the thiazole antibiotics did not affect the transcriptional activity of other transcription factors studied, suggesting that they may specifically target FoxM1. RESULTS/ CONCLUSION: Treatment of human cancer cell lines of different origins with thiazole antibiotics led to apoptosis and downregulation of FoxM1. Our data suggest that thiazole antibiotics that inhibit FoxM1 may be promising drugs against human neoplasia.
BACKGROUND: The oncogenic transcription factor forkhead box M1 (FoxM1) is upregulated in a wide range of different carcinomas, while its expression is turned off in terminally differentiated cells. In addition, FoxM1 is involved in tumor invasion, angiogenesis and metastasis. For these reasons, FoxM1 is an appealing target for anticancer therapeutics. OBJECTIVE/ METHODS: In the quest to develop novel anticancer drugs we decided to target oncogenic transcription factor FoxM1 in tumor cells. Using a cell-based screening system we isolated the thiazole antibiotic siomycin A as inhibitor of FoxM1 transcriptional activity. In addition, we found that because of FoxM1 positive-autoregulation loop siomycin A and another thiazole antibiotic thiostrepton inhibit not only FoxM1 transcriptional activity but also its expression. However, the thiazole antibiotics did not affect the transcriptional activity of other transcription factors studied, suggesting that they may specifically target FoxM1. RESULTS/ CONCLUSION: Treatment of humancancer cell lines of different origins with thiazole antibiotics led to apoptosis and downregulation of FoxM1. Our data suggest that thiazole antibiotics that inhibit FoxM1 may be promising drugs against humanneoplasia.
Authors: Vladimir Petrovic; Robert H Costa; Lester F Lau; Pradip Raychaudhuri; Angela L Tyner Journal: Cancer Biol Ther Date: 2010-06-06 Impact factor: 4.742
Authors: Yirong Li; Martin Ligr; James P McCarron; Garrett Daniels; David Zhang; Xin Zhao; Fei Ye; Jinhua Wang; Xiaomei Liu; Iman Osman; Simon K Mencher; Hebert Lepor; Long G Wang; Anna Ferrari; Peng Lee Journal: Clin Cancer Res Date: 2011-05-23 Impact factor: 12.531