Mithramycin A (Plicamycin), a DNA-binding antitumor antibiotic, is a selective specificity protein 1 (Sp1) inhibitor, which inhibits the growth of various cancers by decreasing Sp1 protein. Specificity protein 1 (Sp1) is a zinc-finger transcription factor that regulates multiple cellular functions and promotes tumor progression.

Mithramycin A decreases Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. Mithramycin A inhibits HEp-2 (50, 100, 200nM) and KB cell (20, 40, 80nM) growth in a concentration-dependent manner after 48 h. Apoptotic cell death is qualitatively estimated by DAPI staining for nuclear condensation and fragmentation. Mithramycin A leads to significant DNA fragmentation compared to untreated controls [1].

The antitumor activity of Mithramycin A (0.2mg/kg/day) was measured in a xenograft model and the reduction in tumor volume and weight was observed. No significant weight loss was observed in mice treated with Mithramycin A, suggesting that Mithramycin A-associated toxicity was minimal. Mithramycin A also increased TUNEL positive cells in tumor xenografts. No significant intergroup differences were observed in the organs, suggesting no significant signs of systemic toxicity at the dose of Mithramycin A used in this study [1].