Thiazole antibiotics target FoxM1 and induce apoptosis in human cancer cells.
Forkhead box M1 (FoxM1) oncogenic transcription factor represents an attractive therapeutic target in the fight against cancer, because it is overexpressed in a majority of human tumors. Recently, using a cell-based assay system we identified thiazole antibiotic Siomycin A as an inhibitor of FoxM1 transcriptional activity. Here, we report that structurally similar thiazole antibiotic, thiostrepton also inhibits the transcriptional activity of FoxM1. Furthermore, we found that these thiopeptides did not inhibit the transcriptional activity of other members of the Forkhead family or some non-related transcription factors. Further experiments revealed that thiazole antibiotics also inhibit FoxM1 expression, but not the expression of other members of the Forkhead box family. In addition, we found that the thiazole antibiotics efficiently inhibited the growth and induced potent apoptosis in human cancer cell lines of different origin. Thiopeptide-induced apoptosis correlated with the suppression of FoxM1 expression, while overexpression of FoxM1 partially protected cancer cells from the thiazole antibiotic-mediated cell death. These data suggest that Siomycin A and thiostrepton may specifically target FoxM1 to induce apoptosis in cancer cells and FoxM1 inhibitors/thiazole antibiotics could be potentially developed as novel anticancer drugs against human neoplasia.
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Uppoor G
UG
Bhat
Marianna
M
Halasi
Andrei L
AL
Gartel
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D010455:Peptides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D013883:Thiostrepton / Q000494:pharmacology
D000900:Anti-Bacterial Agents; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D010455:Peptides; D013844:Thiazoles; C024711:siomycin A; D013883:Thiostrepton