Mithramycin A is a DNA-binding, anti-tumor and neuroprotective antibiotic originally isolated from S. grieseus that has long been used as a chemotherapeutic agent. It mediates its protective function, in part, by regulating acetylation of histones or transcription factors and, thereby, chromatin accessibility to transcriptional machinery. As a selective Sp1 inhibitor, mithramycin A binds to GC rich DNA sequences, displacing Sp1 transcription factor binding to oncogene promoters, which inhibits their expression. Mithramycin A (at 10-200 nM) can sensitize tumor cells to TRAIL-induced apoptosis and has been used to selectively target tumor cells in many different cancer models.
