Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1

The oncogenic transcription factor forkhead box Ml (FoxMl) is overexpressed in a number of different carcinomas, whereas its expression is turned off in terminally differentiated cells. For this reason, FoxMl 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 FoxMl. Interestingly, we observed that Siomycin A was able to down-regulate the transcriptional activity as well as the protein and mRNA abundance of FoxMl. Consequently, we found that the downstream target genes of FoxMl, such as Cdc25B, Sarvivin, and CENPB, were repressed. Also, we observed that consistent with earlier reports of FoxMl inhibition, Siomycin A was able to reduce anchorage-independent growth of cells in soft agar. Furthermore, we found that Siomycin A was able to induce apoptosis selectively in transformed but not normal cells of the same origin. Taken together, our data suggest that FoxMl inhibitor Siomycin A could represent a useful starting point for the development of anticancer therapeutics.